@article {2025|2170, title = {Across (Conformational) Space and (Relaxation) Time: Using Coarse-Grain Simulations to Probe the Intra- and Interdomain Dynamics of the Tau Protein.}, journal = {J Phys Chem B}, volume = {129}, year = {2025}, month = {2025 Nov 27}, pages = {12146-12158}, abstract = {

The biological importance of intrinsically disordered proteins (IDPs) has been established for over two decades, yet these systems remain difficult to characterize, as they are better described by conformational ensembles instead of a single reference structure for their folded counterparts. Tau is a prominent member of the IDP family, which sees its cellular function regulated by multiple phosphorylation sites and whose hyperphosphorylation is involved in neurodegenerative diseases such as Alzheimer\&$\#$39;s. We used coarse-grain MD simulations with the CALVADOS model to investigate the conformational landscape of tau without and with phosphorylations. Characterizing the local compactness of IDPs allows us to highlight how disorder comes in various flavors, as we can define different domains along the tau sequence. We define the IDP\&$\#$39;s Statistical Tertiary Organization (STO) as the average spatial arrangements of domains, which constitute an extension of the tertiary structure of folded proteins. We also use IDP-specific metrics to characterize the local curvature and flexibility of tau. Comparing the local flexibilities with T2 relaxation times from NMR experiments, we show how this metric is related to the protein dynamics. A curvature and flexibility pattern in the repeat domains can also be connected to tau binding properties, without having to explicitly model the protein\&$\#$39;s interaction partner. Finally, we rediscuss the original paperclip model that describes the spatial organization of tau and how phosphorylations impact it. The resulting changes in the protein intradomain and interdomain interaction pattern allow us to propose experimental setups to test our hypothesis.

}, keywords = {Humans, Intrinsically Disordered Proteins, Molecular Dynamics Simulation, Phosphorylation, Protein Conformation, Protein Domains, tau Proteins}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.5c06282}, author = {Marien, Jules and Pr{\'e}vost, Chantal and S Sacquin-Mora} } @article {2025, title = {Impact of Multiple Phosphorylations on the Tau-R2/Tubulin Interface.}, journal = {Biochemistry}, volume = {64}, year = {2025}, month = {2025 Jul 01}, pages = {2916-2925}, abstract = {

The phosphorylation of the microtubule-associated tau protein plays a key role in the regulation of its physiological function. In particular, tau hyperphosphorylation affects its binding to the tubulin surface, destabilizing the tau-microtubule interface and leading to the accumulation of fibrillar aggregates in the brain. In this work, we performed classical molecular dynamics simulations for the tau-R2/tubulin assembly with various phosphorylation states of serines 285, 289, and 293. We analyze the resulting trajectories to obtain a detailed view of the protein interface in the complex and the impact of tau phosphorylations on the stability of this assembly and on the mobility of the tubulin disordered C-terminal tails (CTTs). We show how the tubulin CTTs help maintain the tau-R2 fragment on the tubulin surface despite the destabilizing effect induced by phosphorylations. Conversely, tau phosphorylation affects the CTTs\&$\#$39; flexibility and their potential activity as MAP-recruiting hooks. Furthermore, counterion-mediated bridges between the phosphate groups and tubulin glutamates also contribute to the binding of tau-R2 on the MT. Overall, the complex dynamics of this fuzzy phosphorylated assembly shed new light on the importance of the cytoplasmic environment in neurons in the context of Alzheimer\&$\#$39;s disease.

}, keywords = {Humans, Microtubules, Molecular Dynamics Simulation, Phosphorylation, Protein Binding, tau Proteins, Tubulin}, issn = {1520-4995}, doi = {10.1021/acs.biochem.5c00109}, author = {Marien, Jules and Pr{\'e}vost, Chantal and S Sacquin-Mora} } @article {2025|2171, title = {Sticky Salts: Overbinding of Monovalent Cations to Phosphorylations in All-Atom Force Fields.}, journal = {J Chem Inf Model}, year = {2025}, month = {2025 Dec 05}, abstract = {

Phosphorylation is a major post-translational modification that is involved in the regulation of the dynamics and function of intrinsically disordered proteins (IDPs). We recently characterized a phenomenon, which we termed -phosphate collaborations (P-collabs), where bulk cations form stable bridges between several phosphoresidues in all-atom molecular dynamic simulations. P-collabs were found to be sensitive to the combination of force fields and cation types. Here, we attempt to assess the physical relevance of these P-collabs by evaluating the strength of the cation/phosphate interaction through osmotic coefficient (ϕ) calculations on the model 2NaHPO and 2KHPO salts, using different classical force fields for phosphorylations. All force fields were found to overestimate the strength of the interaction to various degrees. We thus designed new parameters for CHARMM36m and AmberFF99SB-ILDN using the Electronic Continuum Correction (ECC) approach, which provide remarkable agreement for ϕ values for both cation types and over a range of concentrations. We provide a preliminary test of these ECC parameters for phosphorylations by simulating the 7-fold-phosphorylated rhodopsin peptide 7PP and comparing secondary chemical shifts to experimental data. Conformational ensembles resulting from the ECC-derived phosphorylated force fields display both qualitative and quantitative improvements with regard to full-charge force fields. We thus conclude that long-lasting P-collabs are artifacts for classical force fields born from the lack of explicit polarization, and propose a possible computational strategy for the extensive parametrization of phosphorylations. The presence of long-lived P-collabs in simulations produced using classical force fields is therefore a serious concern for the accurate modeling of multiphosphorylated peptides and IDPs, which are at the center of research questions regarding neurodegenerative diseases such as Alzheimer\&$\#$39;s or Parkinson\&$\#$39;s.

}, issn = {1549-960X}, doi = {10.1021/acs.jcim.5c02154}, author = {Marien, Jules and Puyo-Fourtine, Julie and Pr{\'e}vost, Chantal and S Sacquin-Mora and Dubou{\'e}-Dijon, Elise} } @article {2024|2168, title = {The characterization of ancient Methanococcales malate dehydrogenases reveals that strong thermal stability prevents unfolding under intense γ-irradiation}, journal = {Mol. Biol. Evol.}, volume = {41}, year = {2024}, abstract = {

Malate dehydrogenases (MalDHs) (EC.1.1.1.37), which are involved in the conversion of oxaloacetate to pyruvate in the tricarboxylic acid cycle, are a relevant model for the study of enzyme evolution and adaptation. Likewise, a recent study showed that Methanococcales, a major lineage of Archaea, is a good model to study the molecular processes of proteome thermoadaptation in prokaryotes. Here, we use ancestral sequence reconstruction and paleoenzymology to characterize both ancient and extant MalDHs. We observe a good correlation between inferred optimal growth temperatures and experimental optimal temperatures for activity (A-Topt). In particular, we show that the MalDH present in the ancestor of Methanococcales was hyperthermostable and had an A-Topt of 80 \°C, consistent with a hyperthermophilic lifestyle. This ancestor gave rise to two lineages with different thermal constraints: one remained hyperthermophilic, while the other underwent several independent adaptations to colder environments. Surprisingly, the enzymes of the first lineage have retained a thermoresistant behavior (i.e. strong thermostability and high A-Topt), whereas the ancestor of the second lineage shows a strong thermostability, but a reduced A-Topt. Using mutants, we mimic the adaptation trajectory toward mesophily and show that it is possible to significantly reduce the A-Topt without altering the thermostability of the enzyme by introducing a few mutations. Finally, we reveal an unexpected link between thermostability and the ability to resist γ-irradiation-induced unfolding.

}, keywords = {ancestral sequence reconstruction, COaLA evolutionary model, extremophiles, irradiation, reactive oxygen species, thermal adaptation}, author = {Madern, Dominique and Halgand, Fr{\'e}d{\'e}ric and Hou{\'e}e-Levin, Chantal and Dufour, Anne-B{\'e}atrice and Coquille, Sandrine and Ansanay-Alex, Salom{\'e} and S Sacquin-Mora and Brochier-Armanet, C{\'e}line} } @article {2024|2167, title = {NP-collabs: Investigating counterion-mediated bridges in the multiply phosphorylated tau-R2 repeat}, journal = {J. Chem. Inf. Model.}, volume = {64}, year = {2024}, pages = {6570{\textendash}6582}, abstract = {

Tau is an intrinsically disordered (IDP) microtubule-associated protein (MAP) that plays a key part in microtubule assembly and organization. The function of tau can be regulated by multiple phosphorylation sites. These post-translational modifications are known to decrease the binding affinity of tau for microtubules, and abnormal tau phosphorylation patterns are involved in Alzheimer\&$\#$39;s disease. Using all-atom molecular dynamics simulations, we compared the conformational landscapes explored by the tau R2 repeat domain (which comprises a strong tubulin binding site) in its native state and with multiple phosphorylations on the S285, S289, and S293 residues, with four different standard force field (FF)/water model combinations. We find that the different parameters used for the phosphate groups (which can be more or less flexible) in these FFs and the specific interactions between bulk cations and water lead to the formation of a specific type of counterion bridge, termed nP-collab (for nphosphate collaboration, with n being an integer), where counterions form stable structures binding with two or three phosphate groups simultaneously. The resulting effect of nP-collabs on the tau-R2 conformational space differs when using sodium or potassium cations and is likely to impact the peptide overall dynamics and how this MAP interacts with tubulins. We also investigated the effect of phosphoresidue spacing and ionic concentration by modeling polyalanine peptides containing two phosphoserines located one-six residues apart. Three new metrics specifically tailored for IDPs (proteic Menger curvature, local curvature, and local flexibility) were introduced, which allow us to fully characterize the impact of nP-collabs on the dynamics of disordered peptides at the residue level.

}, author = {Marien, Jules and Pr{\'e}vost, Chantal and S Sacquin-Mora} } @article {2024, title = {A Perspective on the Prospective Use of AI in Protein Structure Prediction}, journal = {J Chem Inf Model}, volume = {64}, year = {2024}, month = {Jan}, pages = {26{\textendash}41}, author = {Versini, R. and Sritharan, S. and Aykac Fas, B. and Tubiana, T. and Aimeur, S. Z. and Henri, J. and Erard, M. and N{\"u}sse, O. and Andreani, J. and Baaden, M. and Fuchs, P. and Galochkina, T. and Chatzigoulas, A. and Cournia, Z. and Santuz, H. and S Sacquin-Mora and Taly, A.} } @article {2024|2169, title = {Structural profiles of the full phagocyte NADPH oxidase unveiled by combining computational biology and experimental knowledge}, journal = {J. Biol. Chem.}, volume = {300}, year = {2024}, pages = {107943}, abstract = {

The phagocyte NADPH oxidase (NOX2) is an enzyme, crucial for innate immune defense, producing reactive oxygen species necessary for pathogen destruction. Its activation requires the assembly of soluble proteins (p47phox, p40phox, p67phox, and Rac) with the membrane-bound flavocytochrome b558 (cytb558). We combined circular-dichroism analyses, with decades of experimental data, to filter structural models of the NADPH oxidase complex generated by the artificial intelligence program AlphaFold2 (AF2). The predicted patterns tend to closely resemble the active states of the proteins, as shown by the compact structure of the cytb558, whose dehydrogenase domain is stabilized closer to the membrane. The modeling of the interaction of p47phox with cytb558, which is the initial assembly and activation steps of the NADPH oxidase, enables us to describe how the C terminus of p47phox interacts with the cytb558. Combining the AF2 cytb558-p47phox model and its classical molecular dynamics simulations, we highlighted new hydrophobic lipid insertions of p47phox, particularly at residues Trp80-Phe81 of its PX domain. The AF2 models also revealed the implications of intrinsically disordered regions, such as the fragment between the PX domain and the SH3 regions of p47phox, in ensuring distant protein-protein and membrane-protein interactions. Finally, the AF2 prediction of the cytb558-Trimera model highlighted the importance of leaving Rac1 as a separate protein to reach an active state of the NADPH oxidase complex. Altogether, our step-by-step approach provides a structural model of the active complex showing how disordered regions and specific lipid and protein interactions can enable and stabilize the multisubunit assembly.

}, keywords = {alphafold, Circular Dichroism, Computational biology, lipid-protein interaction, membrane protein, molecular modeling, NADPH oxidase, NOX2, p47(phox), p67(phox), protein assembly, trimera}, author = {Aimeur, Sana and Fas, Burcu Aykac and Serfaty, Xavier and Santuz, Hubert and S Sacquin-Mora and Bizouarn, Tania and Taly, Antoine and Baciou, Laura} } @article {2023|2163, title = {Best Practices of Using AI-Based Models in Crystallography and Their Impact in Structural Biology}, journal = {J Chem Inf Model}, year = {2023}, month = {Jun}, author = {Graille, M and S Sacquin-Mora and Antoine Taly} } @article {2023, title = {Conformational and mechanical stability of the isolated large subunit of membrane-bound [NiFe]-hydrogenase from Cupriavidus necator}, journal = {Frontiers in Microbiology}, volume = {13}, year = {2023}, abstract = {

Comprising at least a bipartite architecture, the large subunit of [NiFe]-hydrogenase harbors the catalytic nickel\–iron site while the small subunit houses an array of electron-transferring Fe-S clusters. Recently, some [NiFe]-hydrogenase large subunits have been isolated showing an intact and redox active catalytic cofactor. In this computational study we have investigated one of these metalloproteins, namely the large subunit HoxG of the membrane-bound hydrogenase from Cupriavidus necator (CnMBH), targeting its conformational and mechanical stability using molecular modelling and long all-atom Gaussian accelerated molecular dynamics (GaMD). Our simulations predict that isolated HoxG is stable in aqueous solution and preserves a large portion of its mechanical properties, but loses rigidity in regions around the active site, in contrast to the MBH heterodimer. Inspired by biochemical data showing dimerization of the HoxG protein and IR measurements revealing an increased stability of the [NiFe] cofactor in protein preparations with higher dimer content, corresponding simulations of homodimeric forms were also undertaken. While the monomeric subunit contains several flexible regions, our data predicts a regained rigidity in homodimer models. Furthermore, we computed the electrostatic properties of models obtained by enhanced sampling with GaMD, which displays a significant amount of positive charge at the protein surface, especially in solvent-exposed former dimer interfaces. These data offer novel insights on the way the [NiFe] core is protected from de-assembly and provide hints for enzyme anchoring to surfaces, which is essential information for further investigations on these minimal enzymes.

}, issn = {1664-302X}, doi = {10.3389/fmicb.2022.1073315}, url = {https://www.frontiersin.org/articles/10.3389/fmicb.2022.1073315}, author = {Dragelj, Jovan and Karafoulidi-Retsou, Chara and Katz, Sagie and Lenz, Oliver and Zebger, Ingo and Caserta, Giorgio and S Sacquin-Mora and Mroginski, Maria Andrea} } @article {2023|2162, title = {Editorial: In Celebration of Women in Science: Biological Modeling and Simulation}, journal = {Front Mol Biosci}, volume = {10}, year = {2023}, pages = {1175325}, author = {Aykac Fas, B and S Sacquin-Mora and Papaleo, E} } @article {2023|2166, title = {It Takes Tau to Tango: Investigating the Fuzzy Interaction between the R2-Repeat Domain and Tubulin C-Terminal Tails}, journal = {Biochemistry}, volume = {62}, year = {2023}, month = {Aug}, pages = {2492{\textendash}2502}, author = {Marien, J and Prevost, C and S Sacquin-Mora} } @article {2022, title = {Between Two Walls: Modeling the Adsorption Behavior of β-Glucosidase A on Bare and SAM-Functionalized Gold Surfaces.}, journal = {Langmuir}, volume = {38}, year = {2022}, month = {2022 Feb 01}, pages = {1313-1323}, abstract = {

The efficient immobilization of enzymes on surfaces remains a complex but central issue in the biomaterials field, which requires us to understand this process at the atomic level. Using a multiscale approach combining all-atom molecular dynamics and coarse-grain Brownian dynamics simulations, we investigated the adsorption behavior of β-glucosidase A (βGA) on bare and self-assembled monolayer (SAM)-functionalized gold surfaces. We monitored the enzyme position and orientation during the molecular dynamics (MD) trajectories and measured the contacts it forms with both surfaces. While the adsorption process has little impact on the protein conformation, it can nonetheless perturb its mechanical properties and catalytic activity. Our results show that compared to the SAM-functionalized surface, the adsorption of βGA on bare gold is more stable, but less specific, and more likely to disrupt the enzyme\&$\#$39;s function. This observation emphasizes the fact that the structural organization of proteins at the solid interface is a key point when designing devices based on enzyme immobilization, as one must find an acceptable stability-activity trade-off.

}, issn = {1520-5827}, doi = {10.1021/acs.langmuir.1c01774}, author = {Bourassin, Nicolas and Barbault, Florent and Marc Baaden and S Sacquin-Mora} } @article {2022|2159, title = {Design {\textendash} a new way to look at old molecules}, journal = {Journal of Integrative Bioinformatics}, volume = {19}, year = {2022}, pages = {20220020}, doi = {doi:10.1515/jib-2022-0020}, url = {https://doi.org/10.1515/jib-2022-0020}, author = {Davide Spalvieri and Anne-Marine Mauviel and Matthieu Lambert and Nicolas F{\'e}rey and S Sacquin-Mora and Matthieu Chavent and Marc Baaden} } @article {2022|2161, title = {Enhanced Sampling Methods for Molecular Dynamics Simulations [Article v1.0]}, journal = {Living Journal of Computational Molecular Science}, volume = {4}, year = {2022}, month = {Dec.}, pages = {1583}, abstract = {

Enhanced sampling algorithms have emerged as powerful methods to extend the utility of molecular dynamics simulations and allow the sampling of larger portions of the configuration space of complex systems in a given amount of simulation time. This review aims to present the unifying principles of and differences between many of the computational methods currently used for enhanced sampling in molecular simulations of biomolecules, soft matter and molecular crystals. In fact, despite the apparent abundance and divergence of such methods, the principles at their core can be boiled down to a relatively limited number of statistical and physical concepts. To enable comparisons, the various methods are introduced using similar terminology and notation. We then illustrate in which ways many different methods combine features of a relatively small number of the same enhanced sampling concepts. This review is intended for scientists with an understanding of the basics of molecular dynamics simulations and statistical physics who want a deeper understanding of the ideas that underlie various enhanced sampling methods and the relationships between them. This living review is intended to be updated to continue to reflect the wealth of sampling methods as they continue to emerge in the literature.

}, doi = {10.33011/livecoms.4.1.1583}, url = {https://livecomsjournal.org/index.php/livecoms/article/view/v4i1e1583}, author = {J{\'e}r{\^o}me H{\'e}nin and Leli{\`e}vre, Tony and Shirts, Michael R. and Valsson, Omar and Delemotte, Lucie} } @article {2022|2150, title = {Modeling the Dynamics of Protein-Protein Interfaces, How and Why?}, journal = {Molecules}, volume = {27}, year = {2022}, pages = {1841}, abstract = {

Protein-protein assemblies act as a key component in numerous cellular processes. Their accurate modeling at the atomic level remains a challenge for structural biology. To address this challenge, several docking and a handful of deep learning methodologies focus on modeling protein-protein interfaces. Although the outcome of these methods has been assessed using static reference structures, more and more data point to the fact that the interaction stability and specificity is encoded in the dynamics of these interfaces. Therefore, this dynamics information must be taken into account when modeling and assessing protein interactions at the atomistic scale. Expanding on this, our review initially focuses on the recent computational strategies aiming at investigating protein-protein interfaces in a dynamic fashion using enhanced sampling, multi-scale modeling, and experimental data integration. Then, we discuss how interface dynamics report on the function of protein assemblies in globular complexes, in fuzzy complexes containing intrinsically disordered proteins, as well as in active complexes, where chemical reactions take place across the protein-protein interface.

}, issn = {1420-3049}, doi = {10.3390/molecules27061841}, url = {https://www.mdpi.com/1420-3049/27/6/1841}, author = {Karaca, Ezgi and Pr{\'e}vost, Chantal and S Sacquin-Mora} } @article {2022|2160, title = {Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation}, journal = {Nature Communications}, volume = {13}, year = {2022}, doi = {10.1038/s41467-022-34813-5}, url = {https://doi.org/10.1038/s41467-022-34813-5}, author = {John T. Petroff and Noah M. Dietzen and Ezry Santiago-McRae and Brett Deng and Maya S. Washington and Lawrence J. Chen and K. Trent Moreland and Zengqin Deng and Michael Rau and James A. J. Fitzpatrick and Peng Yuan and Thomas T. Joseph and J{\'e}r{\^o}me H{\'e}nin and Grace Brannigan and Wayland W. L. Cheng} } @article {2021, title = {Moving pictures: Reassessing docking experiments with a dynamic view of protein interfaces.}, journal = {Proteins}, year = {2021}, month = {2021 May 26}, abstract = {

The modeling of protein assemblies at the atomic level remains a central issue in structural biology, as protein interactions play a key role in numerous cellular processes. This problem is traditionally addressed using docking tools, where the quality of the models is based on their similarity to a single reference experimental structure. However, using a static reference does not take into account the dynamic quality of the protein interface. Here, we used all-atom classical Molecular Dynamics simulations to investigate the stability of the reference interface for three complexes that previously served as targets in the CAPRI competition. For each one of these targets, we also ran MD simulations for ten models that are distributed over the High, Medium and Acceptable accuracy categories. To assess the quality of these models from a dynamic perspective, we set up new criteria which take into account the stability of the reference experimental protein interface. We show that, when the protein interfaces are allowed to evolve along time, the original ranking based on the static CAPRI criteria no longer holds as over 50\% of the docking models undergo a category change (which can be either toward a better or a lower accuracy group) when reassessing their quality using dynamic information.

}, issn = {1097-0134}, doi = {10.1002/prot.26152}, author = {Chantal Pr{\'e}vost and S Sacquin-Mora} } @article {2021|2146, title = {When Order Meets Disorder: Modeling and Function of the Protein Interface in Fuzzy Complexes}, journal = {Biomolecules}, volume = {11}, year = {2021}, pages = {1529}, abstract = {

The degree of proteins structural organization ranges from highly structured, compact folding to intrinsic disorder, where each degree of self-organization corresponds to specific functions: well-organized structural motifs in enzymes offer a proper environment for precisely positioned functional groups to participate in catalytic reactions; at the other end of the self-organization spectrum, intrinsically disordered proteins act as binding hubs via the formation of multiple, transient and often non-specific interactions. This review focusses on cases where structurally organized proteins or domains associate with highly disordered protein chains, leading to the formation of interfaces with varying degrees of fuzziness. We present a review of the computational methods developed to provide us with information on such fuzzy interfaces, and how they integrate experimental information. The discussion focusses on two specific cases, microtubules and homologous recombination nucleoprotein filaments, where a network of intrinsically disordered tails exerts regulatory function in recruiting partner macromolecules, proteins or DNA and tuning the atomic level association. Notably, we show how computational approaches such as molecular dynamics simulations can bring new knowledge to help bridging the gap between experimental analysis, that mostly concerns ensemble properties, and the behavior of individual disordered protein chains that contribute to regulation functions.

}, issn = {2218-273X}, doi = {10.3390/biom11101529}, url = {https://www.mdpi.com/2218-273X/11/10/1529}, author = {S Sacquin-Mora and Chantal Pr{\'e}vost} } @article {2020|2117, title = {Aggregation of disease-related peptides.}, journal = {Prog Mol Biol Transl Sci}, volume = {170}, year = {2020}, month = {2020}, pages = {435-460}, abstract = {

Protein misfolding and aggregation of amyloid proteins is the fundamental cause of more than 20 diseases. Molecular mechanisms of the self-assembly and the formation of the toxic aggregates are still elusive. Computer simulations have been intensively used to study the aggregation of amyloid peptides of various amino acid lengths related to neurodegenerative diseases. We review atomistic and coarse-grained simulations of short amyloid peptides aimed at determining their transient oligomeric structures and the early and late aggregation steps.

}, issn = {1878-0814}, doi = {10.1016/bs.pmbts.2019.12.002}, author = {Phuong Hoang Nguyen and Sterpone, Fabio and Philippe Derreumaux} } @article {2020|2075, title = {Characterization of β-turns by electronic circular dichroism spectroscopy: a coupled molecular dynamics and time-dependent density functional theory computational study.}, journal = {Phys Chem Chem Phys}, volume = {22}, year = {2020}, month = {2020 Jan 21}, pages = {1611-1623}, abstract = {

Electronic circular dichroism is one of the most used spectroscopic techniques for peptide and protein structural characterization. However, while valuable experimental spectra exist for α-helix, β-sheet and random coil secondary structures, previous studies showed important discrepancies for β-turns, limiting their use as a reference for structural studies. In this paper, we simulated circular dichroism spectra for the best-characterized β-turns in peptides, namely types I, II, I\&$\#$39; and II\&$\#$39;. In particular, by combining classical molecular dynamics simulations and state-of-the-art quantum time-dependent density functional theory (with the polarizable embedding multiscale model) computations, two common electronic circular dichroism patterns were found for couples of β-turn types (namely, type I/type II\&$\#$39; and type II/type I\&$\#$39;), at first for a minimal di-peptide model (Ace-Ala-Ala-NHMe), but also for all sequences tested with non-aromatic residues in the central positions. On the other hand, as expected, aromatic substitution causes important perturbations to the previously found ECD patterns. Finally, by applying suitable approximations, these patterns were subsequently rationalized based on the exciton chirality rule. All these results provide useful predictions and pave the way for a possible experimental characterization of β-turns based on circular dichroism spectroscopy.

}, keywords = {Circular Dichroism, Computational Chemistry, Computer Simulation, Molecular Dynamics Simulation, Protein Conformation, beta-Strand, Protein Structure, Tertiary}, issn = {1463-9084}, doi = {10.1039/c9cp05776e}, author = {Migliore, Mattia and Bonvicini, Andrea and Tognetti, Vincent and Guilhaudis, Laure and Marc Baaden and Oulyadi, Hassan and Joubert, Laurent and S{\'e}galas-Milazzo, Isabelle} } @article {2020|2144, title = {Implicit Modeling of the Impact of Adsorption on Solid Surfaces for Protein Mechanics and Activity with a Coarse-Grained Representation}, journal = {J Phys Chem B}, volume = {124}, year = {2020}, month = {Oct}, pages = {8516{\textendash}8523}, author = {Bourassin, N. and Marc Baaden and Lojou, E. and S Sacquin-Mora} } @article {2020, title = {Protein Interaction Energy Landscapes are Shaped by Functional and also Non-functional Partners.}, journal = {J Mol Biol}, volume = {432}, year = {2020}, month = {2020 Feb 14}, pages = {1183-1198}, abstract = {

In the crowded cell, a strong selective pressure operates on the proteome to limit the competition between functional and non-functional protein-protein interactions. We developed an original theoretical framework in order to interrogate how this competition constrains the behavior of proteins with respect to their partners or random encounters. Our theoretical framework relies on a two-dimensional (2D) representation of interaction energy landscapes, with 2D energy maps, which reflect in a synthetic way the spatial distribution of the interaction propensity of a protein surface for another protein. We realized the interaction propensity mapping of proteins\&$\#$39; surfaces in interaction with functional and arbitrary partners and asked whether the distribution of their interaction propensity is conserved during evolution. Therefore, we performed several thousands of cross-docking simulations to systematically characterize the energy landscapes of 103 proteins interacting with different sets of homologs, corresponding to their functional partner\&$\#$39;s family or arbitrary protein families. Then, we systematically compared the energy maps resulting from the docking of each protein with the different protein families of the dataset. Strikingly, we show that the interaction propensity not only of the binding sites but also of the rest of the surface is conserved for docking partners belonging to the same protein family. Interestingly, this observation holds for docked proteins corresponding to true but also arbitrary partners. Our theoretical framework enables the characterization of the energy behavior of a protein in interaction with hundreds of proteins and opens the way for the characterization of the behavior of proteins in a specific environment.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2019.12.047}, author = {Schweke, Hugo and Mucchielli, Marie-H{\'e}l{\`e}ne and S Sacquin-Mora and Bei, Wanying and Lopes, Anne} } @inbook {2020|2123, title = {Protein thermal stability}, booktitle = {Computational Approaches for Understanding Dynamical Systems: Protein Folding and Assembly}, year = {2020}, author = {S. Timr and D. Madern and F. Sterpone} } @article {2020|2142, title = {Scalable molecular dynamics on CPU and GPU architectures with NAMD}, journal = {The Journal of Chemical Physics}, volume = {153}, year = {2020}, chapter = {044130}, abstract = {

NAMD is a molecular dynamics program designed for high-performance simulations of very large biological objects on CPU- and GPU-based architectures. NAMD offers scalable performance on petascale parallel supercomputers consisting of hundreds of thousands of cores, as well as on inexpensive commodity clusters commonly found in academic environments. It is written in C++ and leans on Charm++ parallel objects for optimal performance on low-latency architectures. NAMD is a versatile, multipurpose code that gathers state-of-the-art algorithms to carry out simulations in apt thermodynamic ensembles, using the widely popular CHARMM, AMBER, OPLS, and GROMOS biomolecular force fields. Here, we review the main features of NAMD that allow both equilibrium and enhanced-sampling molecular dynamics simulations with numerical efficiency. We describe the underlying concepts utilized by NAMD and their implementation, most notably for handling long-range electrostatics; controlling the temperature, pressure, and pH; applying external potentials on tailored grids; leveraging massively parallel resources in multiple-copy simulations; and hybrid quantum-mechanical/molecular-mechanical descriptions. We detail the variety of options offered by NAMD for enhanced-sampling simulations aimed at determining free-energy differences of either alchemical or geometrical transformations and outline their applicability to specific problems. Last, we discuss the roadmap for the development of NAMD and our current efforts toward achieving optimal performance on GPU-based architectures, for pushing back the limitations that have prevented biologically realistic billion-atom objects to be fruitfully simulated, and for making large-scale simulations less expensive and easier to set up, run, and analyze. NAMD is distributed free of charge with its source code at www.ks.uiuc.edu.

}, keywords = {NAMD}, doi = {10.1063/5.0014475}, url = {https://aip.scitation.org/doi/10.1063/5.0014475}, author = {James Phillips and David Hardy and Julio Maia and John Stone and Joao Ribeiro and Rafael Bernardi and Ronak Buch and Giacomo Fiorin and J{\'e}r{\^o}me H{\'e}nin and Wei Jiang and Ryan McGreevy and Melo, Marcelo Cardoso dos Reis and Brian Radak and Robert Skeel and Abhishek Singharoy and Yi Wang and Benoit Roux and Aleksei Aksimentiev and Zan Luthey-Schulten and Laxmikant Kale and Klaus Schulten and Christophe Chipot and Emad Tajkhorshid} } @article {2020|2140, title = {Structural transitions in the RNA 7SK 5{\textquoteright} hairpin and their effect on HEXIM binding}, journal = {Nucleic Acids Res}, volume = {48}, year = {2020}, month = {01}, pages = {373-389}, abstract = {

7SK RNA, as part of the 7SK ribonucleoprotein complex, is crucial to the regulation of transcription by RNA-polymerase II, via its interaction with the positive transcription elongation factor P-TEFb. The interaction is induced by binding of the protein HEXIM to the 5\&$\#$39; hairpin (HP1) of 7SK RNA. Four distinct structural models have been obtained experimentally for HP1. Here, we employ computational methods to investigate the relative stability of these structures, transitions between them, and the effects of mutations on the observed structural ensembles. We further analyse the results with respect to mutational binding assays, and hypothesize a mechanism for HEXIM binding. Our results indicate that the dominant structure in the wild type exhibits a triplet involving the unpaired nucleotide U40 and the base pair A43-U66 in the GAUC/GAUC repeat. This conformation leads to an open major groove with enough potential binding sites for peptide recognition. Sequence mutations of the RNA change the relative stability of the different structural ensembles. Binding affinity is consequently lost if these changes alter the dominant structure.

}, doi = {10.1093/nar/gkz1071}, author = {R{\"o}der, Konstantin and Guillaume Stirnemann and Dock-Bregeon, Anne-Catherine and Wales, David J and Pasquali, Samuela} } @article {2020|2124, title = {Temperature Unmasks Allosteric Propensity in a Thermophilic Malate Dehydrogenase via Dewetting and Collapse}, journal = {The Journal of Physical Chemistry B}, volume = {124}, year = {2020}, pages = {1001-1008}, doi = {10.1021/acs.jpcb.9b10776}, url = {https://doi.org/10.1021/acs.jpcb.9b10776}, author = {Katava, M. and Marchi, M. and Madern, D. and Sztucki, M. and Maccarini, M. and Sterpone, F.} } @article {2020|2141, title = {Water dynamics at electrified graphene interfaces: a jump model perspective}, journal = {Phys Chem Chem Phys}, year = {2020}, month = {Mar}, abstract = {

The reorientation dynamics of water at electrified graphene interfaces was recently shown [J. Phys. Chem. Lett., 2020, 11, 624-631] to exhibit a surprising and strongly asymmetric behavior: positive electrode potentials slow down interfacial water reorientation, while for increasingly negative potentials water dynamics first accelerates before reaching an extremum and then being retarded for larger potentials. Here we use classical molecular dynamics simulations to determine the molecular mechanisms governing water dynamics at electrified interfaces. We show that changes in water reorientation dynamics with electrode potential arise from the electrified interfaces\&$\#$39; impacts on water hydrogen-bond jump exchanges, and can be quantitatively described by the extended jump model. Finally, our simulations indicate that no significant dynamical heterogeneity occurs within the water interfacial layer next to the weakly interacting graphene electrode.

}, doi = {10.1039/d0cp00359j}, author = {Zhang, Yiwei and Guillaume Stirnemann and Hynes, James T and Laage, Damien} } @article {2019|2109, title = {Amyloid-β (29{\textendash}42) Dimeric Conformations in Membranes Rich in Omega-3 and Omega-6 Polyunsaturated Fatty Acids}, journal = {The Journal of Physical Chemistry B}, volume = {123}, year = {2019}, pages = {2687{\textendash}2696}, author = {Lu, Yan and Shi, Xiao-Feng and Phuong Hoang Nguyen and Sterpone, Fabio and Salsbury Jr, Freddie R and Philippe Derreumaux} } @article {2019|2061, title = {Coarse-grain simulations on NMR conformational ensembles highlight functional residues in proteins.}, journal = {J R Soc Interface}, volume = {16}, year = {2019}, month = {2019 Jul 26}, pages = {20190075}, abstract = {

Dynamics are a key feature of protein function, and this is especially true of gating residues, which occupy cavity or tunnel lining positions in the protein structure, and will reversibly switch between open and closed conformations in order to control the diffusion of small molecules within a protein\&$\#$39;s internal matrix. Earlier work on globins and hydrogenases have shown that these gating residues can be detected using a multiscale scheme combining all-atom classic molecular dynamics simulations and coarse-grain calculations of the resulting conformational ensemble mechanical properties. Here, we show that the structural variations observed in the conformational ensembles produced by NMR spectroscopy experiments are sufficient to induce noticeable mechanical changes in a protein, which in turn can be used to identify residues important for function and forming a mechanical nucleus in the protein core. This new approach, which combines experimental data and rapid coarse-grain calculations and no longer needs to resort to time-consuming all-atom simulations, was successfully applied to five different protein families.

}, issn = {1742-5662}, doi = {10.1098/rsif.2019.0075}, author = {S Sacquin-Mora} } @article {2019|2060, title = {Conformational Stability Adaptation of a Double-Stranded RNA-Binding Domain to Transfer RNA Ligand.}, journal = {Biochemistry}, volume = {58}, year = {2019}, month = {2019 May 21}, pages = {2463-2473}, abstract = {

The double-stranded RNA-binding domain (dsRBD) is a broadly distributed domain among RNA-maturing enzymes. Although this domain recognizes dsRNA\&$\#$39;s structures via a conserved canonical structure adopting an α-βββ-α topology, several dsRBDs can accommodate discrete structural extensions expanding further their functional repertoire. How these structural elements engage cooperative communications with the canonical structure and how they contribute to the dsRBD\&$\#$39;s overall folding are poorly understood. Here, we addressed these issues using the dsRBD of human dihydrouridine synthase-2 (hDus2) (hDus2-dsRBD) as a model. This dsRBD harbors N- and C-terminal extensions, the former being directly involved in the recognition of tRNA substrate of hDus2. These extensions engage residues that form a long-range hydrophobic network (LHN) outside the RNA-binding interface. We show by coarse-grain Brownian dynamics that the Nt-extension and its residues F359 and Y364 rigidify the major folding nucleus of the canonical structure via an indirect effect. hDus2-dsRBD unfolds following a two-state cooperative model, whereas both F359A and Y364A mutants, designed to destabilize this LHN, unfold irreversibly. Structural and computational analyses show that these mutants are unstable due to an increase in the dynamics of the two extensions favoring solvent exposure of α2-helix and weakening the main folding nucleus rigidity. This LHN appears essential for maintaining a thermodynamic stability of the overall system and eventually a functional conformation for tRNA recognition. Altogether, our findings suggest that functional adaptability of extended dsRBDs is promoted by a cooperative hydrophobic coupling between the extensions acting as effectors and the folding nucleus of the canonical structure.

}, issn = {1520-4995}, doi = {10.1021/acs.biochem.9b00111}, author = {Bou-Nader, Charles and Pecqueur, Ludovic and Barraud, Pierre and Fontecave, Marc and Tisn{\'e}, Carine and S Sacquin-Mora and Hamdane, Djemel} } @article {2019|2070, title = {Design games and game design: Relations between design, codesign and serious games in adult education}, journal = {From UXD to LivXD: Living eXperience Design}, year = {2019}, pages = {229{\textendash}253}, author = {Alvarez, Julian and Irrmann, Olivier and Djaouti, Damien and Antoine Taly and Rampnoux, Olivier and Sauv{\'e}, Louise} } @article {2019|2139, title = {Effect of Ions on Water Dynamics in Dilute and Concentrated Aqueous Salt Solutions}, journal = {J Phys Chem B}, volume = {123}, year = {2019}, month = {Apr}, pages = {3312-3324}, abstract = {

Aqueous ionic solutions are ubiquitous in chemistry and in biology. Experiments show that ions affect water dynamics, but a full understanding of several questions remains needed: why some salts accelerate water dynamics while others slow it down, why the effect of a given salt can be concentration-dependent, whether the effect of ions is rather local or more global. Numerical simulations are particularly suited to disentangle these different effects, but current force fields suffer from limitations and often lead to a poor description of dynamics in several aqueous salt solutions. Here, we develop an improved classical force field for the description of alkali halides that yields dynamics in excellent agreement with experimental measurements for water reorientational and translational dynamics. These simulations are analyzed with an extended jump model, which allows to compare the effects of ions on local hydrogen-bond exchange dynamics and on more global properties like viscosity. Our results unambiguously show that the ion-induced changes in water dynamics are usually mostly due to a local effect on the hydrogen-bond exchange dynamics; in contrast, the change in viscosity leads to a smaller effect, which governs the retardation only for a minority of salts and at high concentrations. We finally show how the respective importance of these two effects can be directly determined from experimental measurements alone, thus providing guidelines for the selection of an electrolyte with specific dynamical properties.

}, doi = {10.1021/acs.jpcb.9b01053}, author = {Laage, Damien and Guillaume Stirnemann} } @article {2019|2067, title = {An inter-dimer allosteric switch controls NMDA receptor activity}, journal = {The EMBO journal}, volume = {38}, year = {2019}, author = {Esmenjaud, Jean-Baptiste and Stroebel, David and Chan, Kelvin and Grand, Teddy and David, M{\'e}lissa and Wollmuth, Lonnie P and Antoine Taly and Paoletti, Pierre} } @article {2019|2071, title = {Involvement of the GABAA receptor α subunit in the mode of action of etifoxine}, journal = {Pharmacological research}, volume = {145}, year = {2019}, pages = {104250}, author = {Mattei, C{\'e}sar and Antoine Taly and Soualah, Zineb and Saulais, Oph{\'e}lie and Henrion, Daniel and Gu{\'e}rineau, Nathalie C and Verleye, Marc and Legros, Christian} } @article {2019|2118, title = {Mesoscale biosimulations within a unified framework: from proteins to plasmids}, year = {2019}, pages = {1-12}, author = {P. Maiocchi and Philippe Derreumaux and F. Sterpone and S. Melchionna} } @article {2019|2122, title = {Modelling lipid systems in fluid with Lattice Boltzmann Molecular Dynamics simulations and hydrodynamics}, journal = {Scientific Reports}, volume = {9}, year = {2019}, pages = {16450}, abstract = {

In this work we present the coupling between Dry Martini, an efficient implicit solvent coarse-grained model for lipids, and the Lattice Boltzmann Molecular Dynamics (LBMD) simulation technique in order to include naturally hydrodynamic interactions in implicit solvent simulations of lipid systems. After validating the implementation of the model, we explored several systems where the action of a perturbing fluid plays an important role. Namely, we investigated the role of an external shear flow on the dynamics of a vesicle, the dynamics of substrate release under shear, and inquired the dynamics of proteins and substrates confined inside the core of a vesicle. Our methodology enables future exploration of a large variety of biological entities and processes involving lipid systems at the mesoscopic scale where hydrodynamics plays an essential role, e.g. by modulating the migration of proteins in the proximity of membranes, the dynamics of vesicle-based drug delivery systems, or, more generally, the behaviour of proteins in cellular compartments.

}, isbn = {2045-2322}, doi = {10.1038/s41598-019-52760-y}, url = {https://doi.org/10.1038/s41598-019-52760-y}, author = {F. Brandner, Astrid and Timr, Stepan and Melchionna, Simone and Philippe Derreumaux and Marc Baaden and Sterpone, Fabio} } @article {2019|2120, title = {Multiscale Aggregation of the Amyloid Aβ16{\textendash}22 Peptide: From Disordered Coagulation and Lateral Branching to Amorphous Prefibrils}, journal = {The Journal of Physical Chemistry Letters}, volume = {10}, year = {2019}, pages = {1594-1599}, doi = {10.1021/acs.jpclett.9b00423}, url = {https://doi.org/10.1021/acs.jpclett.9b00423}, author = {Chiricotto, Mara and Melchionna, Simone and Philippe Derreumaux and Sterpone, Fabio} } @article {2019|2121, title = {OPEP6: A New Constant-pH Molecular Dynamics Simulation Scheme with OPEP Coarse-Grained Force Field}, journal = {Journal of Chemical Theory and Computation}, volume = {15}, year = {2019}, pages = {3875-3888}, doi = {10.1021/acs.jctc.9b00202}, url = {https://doi.org/10.1021/acs.jctc.9b00202}, author = {Barroso da Silva, Fernando Luis and Sterpone, Fabio and Philippe Derreumaux} } @conference {2019|2099, title = {QuickSES: A Library for Fast Computation of Solvent Excluded Surfaces}, booktitle = {Workshop on Molecular Graphics and Visual Analysis of Molecular Data}, year = {2019}, publisher = {The Eurographics Association}, organization = {The Eurographics Association}, isbn = {978-3-03868-085-7}, doi = {10.2312/molva.20191095}, author = {Martinez, Xavier and Krone, Michael and Marc Baaden}, editor = {Byska, Jan and Krone, Michael and Sommer, Bj{\"o}rn} } @article {2019|2119, title = {Stability Effect of Quinary Interactions Reversed by Single Point Mutations}, journal = {Journal of the American Chemical Society}, volume = {141}, year = {2019}, pages = {4660-4669}, doi = {10.1021/jacs.8b13025}, url = {https://doi.org/10.1021/jacs.8b13025}, author = {Gnutt, David and Timr, Stepan and Ahlers, Jonas and K{\"o}nig, Benedikt and Manderfeld, Emily and Heyden, Matthias and Sterpone, Fabio and Ebbinghaus, Simon} } @article {2018|2086, title = {Analyzing protein topology based on Laguerre tessellation of a pore-traversing water network.}, journal = {Sci Rep}, volume = {8}, year = {2018}, month = {2018 09 10}, pages = {13540}, abstract = {

Given the tight relation between protein structure and function, we present a set of methods to analyze protein topology, implemented in the VLDP program, relying on Laguerre space partitions built from series of molecular dynamics snapshots. The Laguerre partition specifies inter-atomic contacts, formalized in graphs. The deduced properties are the existence and count of water aggregates, possible passage ways and constrictions, the structure, connectivity, stability and depth of the water network. As a test-case, the membrane protein FepA is investigated in its full environment, yielding a more precise description of the protein surface. Inside FepA, the solvent splits into isolated clusters and an intricate network connecting both sides of the lipid bilayer. The network is dynamic, connections set on and off, occasionally substantially relocating traversing paths. Subtle differences are detected between two forms of FepA, ligand-free and complexed with its natural iron carrier, the enterobactin. The complexed form has more constricted and more centered openings in the upper part whereas, in the lower part, constriction is released: two main channels between the plug and barrel lead directly to the periplasm. Reliability, precision and the variety of topological features are the main interest of the method.

}, keywords = {Bacterial Outer Membrane Proteins, Carrier Proteins, Enterobactin, Molecular Dynamics Simulation, Protein Stability, Protein Structure, Secondary, Receptors, Cell Surface, Structure-Activity Relationship, Water}, issn = {2045-2322}, doi = {10.1038/s41598-018-31422-5}, author = {Esque, J{\'e}r{\'e}my and Sansom, Mark S P and Marc Baaden and Oguey, Christophe} } @inbook {2018|2085, title = {Applications to water transport systems: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {389-414}, issn = {1364-5498}, doi = {10.1039/c8fd90022a}, author = {Marc Baaden and Barboiu, Mihail and Borthakur, Manash Pratim and Chen, Chun-Long and Coalson, Rob and Davis, Jeffery and Freger, Viatcheslav and Gong, Bing and H{\'e}lix-Nielsen, Claus and Hickey, Robert and Hinds, Bruce and Hirunpinyopas, Wisit and Horner, Andreas and Hou, Jun-Li and Hummer, Gerhard and Iamprasertkun, Pawin and Kazushi, Kinbara and Kumar, Manish and Legrand, Yves-Marie and Lokesh, Mahesh and Mi, Baoxia and Mitra, Sushanta and Murail, Samuel and Noy, Aleksandr and Nunes, Suzana and Pohl, Peter and Song, Qilei and Song, Woochul and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish} } @inbook {2018|2082, title = {Biomimetic water channels: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {205-229}, issn = {1364-5498}, doi = {10.1039/c8fd90020e}, author = {Marc Baaden and Barboiu, Mihail and Bill, Roslyn M and Chen, Chun-Long and Davis, Jeffery and Di Vincenzo, Maria and Freger, Viatcheslav and Fr{\"o}ba, Michael and Gale, Philip A and Gong, Bing and H{\'e}lix-Nielsen, Claus and Hickey, Robert and Hinds, Bruce and Hou, Jun-Li and Hummer, Gerhard and Kumar, Manish and Legrand, Yves-Marie and Lokesh, Mahesh and Mi, Baoxia and Murail, Samuel and Pohl, Peter and Sansom, Mark and Song, Qilei and Song, Woochul and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish and V{\"o}gele, Martin} } @article {2018|2137, title = {Conformational entropy of a single peptide controlled under force governs protease recognition and catalysis}, journal = {Proc Natl Acad Sci U S A}, volume = {115}, year = {2018}, month = {11}, pages = {11525-11530}, abstract = {

An immense repertoire of protein chemical modifications catalyzed by enzymes is available as proteomics data. Quantifying the impact of the conformational dynamics of the modified peptide remains challenging to understand the decisive kinetics and amino acid sequence specificity of these enzymatic reactions in vivo, because the target peptide must be disordered to accommodate the specific enzyme-binding site. Here, we were able to control the conformation of a single-molecule peptide chain by applying mechanical force to activate and monitor its specific cleavage by a model protease. We found that the conformational entropy impacts the reaction in two distinct ways. First, the flexibility and accessibility of the substrate peptide greatly increase upon mechanical unfolding. Second, the conformational sampling of the disordered peptide drives the specific recognition, revealing force-dependent reaction kinetics. These results support a mechanism of peptide recognition based on conformational selection from an ensemble that we were able to quantify with a torsional free-energy model. Our approach can be used to predict how entropy affects site-specific modifications of proteins and prompts conformational and mechanical selectivity.

}, keywords = {enzymology, mechanics, proteases, single molecule, torsional free energy}, doi = {10.1073/pnas.1803872115}, author = {Guerin, Marcelo E and Guillaume Stirnemann and Giganti, David} } @article {2018|2046, title = {Controlling Redox Enzyme Orientation at Planar Electrodes}, journal = {Catalysts}, volume = {8}, year = {2018}, abstract = {

Redox enzymes, which catalyze reactions involving electron transfers in living organisms, are very promising components of biotechnological devices, and can be envisioned for sensing applications as well as for energy conversion. In this context, one of the most significant challenges is to achieve efficient direct electron transfer by tunneling between enzymes and conductive surfaces. Based on various examples of bioelectrochemical studies described in the recent literature, this review discusses the issue of enzyme immobilization at planar electrode interfaces. The fundamental importance of controlling enzyme orientation, how to obtain such orientation, and how it can be verified experimentally or by modeling are the three main directions explored. Since redox enzymes are sizable proteins with anisotropic properties, achieving their functional immobilization requires a specific and controlled orientation on the electrode surface. All the factors influenced by this orientation are described, ranging from electronic conductivity to efficiency of substrate supply. The specificities of the enzymatic molecule, surface properties, and dipole moment, which in turn influence the orientation, are introduced. Various ways of ensuring functional immobilization through tuning of both the enzyme and the electrode surface are then described. Finally, the review deals with analytical techniques that have enabled characterization and quantification of successful achievement of the desired orientation. The rich contributions of electrochemistry, spectroscopy (especially infrared spectroscopy), modeling, and microscopy are featured, along with their limitations.

}, issn = {2073-4344}, doi = {10.3390/catal8050192}, url = {http://www.mdpi.com/2073-4344/8/5/192}, author = {Hitaishi, Vivek Pratap and Clement, Romain and Bourassin, Nicolas and Marc Baaden and de Poulpiquet, Anne and S Sacquin-Mora and Ciaccafava, Alexandre and Lojou, Elisabeth} } @article {2018|2134, title = {DNA Binding Induces a Nanomechanical Switch in the RRM1 Domain of TDP-43}, journal = {J Phys Chem Lett}, volume = {9}, year = {2018}, month = {Jul}, pages = {3800-3807}, abstract = {

Understanding the molecular mechanisms governing protein-nucleic acid interactions is fundamental to many nuclear processes. However, how nucleic acid binding affects the conformation and dynamics of the substrate protein remains poorly understood. Here we use a combination of single molecule force spectroscopy AFM and biochemical assays to show that the binding of TG-rich ssDNA triggers a mechanical switch in the RRM1 domain of TDP-43, toggling between an entropic spring devoid of mechanical stability and a shock absorber bound-form that resists unfolding forces of \∼40 pN. The fraction of mechanically resistant proteins correlates with an increasing length of the TG n oligonucleotide, demonstrating that protein mechanical stability is a direct reporter of nucleic acid binding. Steered molecular dynamics simulations on related RNA oligonucleotides reveal that the increased mechanical stability fingerprinting the holo-form is likely to stem from a unique scenario whereby the nucleic acid acts as a \"mechanical staple\" that protects RRM1 from mechanical unfolding. Our approach highlights nucleic acid binding as an effective strategy to control protein nanomechanics.

}, doi = {10.1021/acs.jpclett.8b01494}, author = {Wang, Yong Jian and Rico-Lastres, Palma and Lezamiz, Ainhoa and Mora, Marc and Solsona, Carles and Guillaume Stirnemann and Garcia-Manyes, Sergi} } @article {2018|2132, title = {The force-dependent mechanism of DnaK-mediated mechanical folding}, journal = {Sci Adv}, volume = {4}, year = {2018}, month = {Feb}, pages = {eaaq0243}, abstract = {

It is well established that chaperones modulate the protein folding free-energy landscape. However, the molecular determinants underlying chaperone-mediated mechanical folding remain largely elusive, primarily because the force-extended unfolded conformation fundamentally differs from that characterized in biochemistry experiments. We use single-molecule force-clamp spectroscopy, combined with molecular dynamics simulations, to study the effect that the Hsp70 system has on the mechanical folding of three mechanically stiff model proteins. Our results demonstrate that, when working independently, DnaJ (Hsp40) and DnaK (Hsp70) work as holdases, blocking refolding by binding to distinct substrate conformations. Whereas DnaK binds to molten globule-like forms, DnaJ recognizes a cryptic sequence in the extended state in an unanticipated force-dependent manner. By contrast, the synergetic coupling of the Hsp70 system exhibits a marked foldase behavior. Our results offer unprecedented molecular and kinetic insights into the mechanisms by which mechanical force finely regulates chaperone binding, directly affecting protein elasticity.

}, doi = {10.1126/sciadv.aaq0243}, author = {Perales-Calvo, Judit and Giganti, David and Guillaume Stirnemann and Garcia-Manyes, Sergi} } @article {2018|2136, title = {Forcing the reversibility of a mechanochemical reaction}, journal = {Nat Commun}, volume = {9}, year = {2018}, month = {08}, pages = {3155}, abstract = {

Mechanical force modifies the free-energy surface of chemical reactions, often enabling thermodynamically unfavoured reaction pathways. Most of our molecular understanding of force-induced reactivity is restricted to the irreversible homolytic scission of covalent bonds and ring-opening in polymer mechanophores. Whether mechanical force can by-pass thermodynamically locked reactivity in heterolytic bimolecular reactions and how this impacts the reaction reversibility remains poorly understood. Using single-molecule force-clamp spectroscopy, here we show that mechanical force promotes the thermodynamically disfavored SN2 cleavage of an individual protein disulfide bond by poor nucleophilic organic thiols. Upon force removal, the transition from the resulting high-energy unstable mixed disulfide product back to the initial, low-energy disulfide bond reactant becomes suddenly spontaneous, rendering the reaction fully reversible. By rationally varying the nucleophilicity of a series of small thiols, we demonstrate how force-regulated chemical kinetics can be finely coupled with thermodynamics to predict and modulate the reversibility of bimolecular mechanochemical reactions.

}, doi = {10.1038/s41467-018-05115-6}, author = {Beedle, Amy E M and Mora, Marc and Davis, Colin T and Snijders, Ambrosius P and Guillaume Stirnemann and Garcia-Manyes, Sergi} } @article {2018|2088, title = {From Virtual Reality to Immersive Analytics in Bioinformatics.}, journal = {J Integr Bioinform}, volume = {15}, year = {2018}, month = {2018 Jul 09}, abstract = {

Bioinformatics-related research produces huge heterogeneous amounts of data. This wealth of information includes data describing metabolic mechanisms and pathways, proteomics, transcriptomics, and metabolomics. Often, the visualization and exploration of related structural - usually molecular - data plays an important role in the aforementioned contexts. For decades, virtual reality (VR)-related technologies were developed and applied to Bioinformatics problems. Often, these approaches provide \"just\" visual support of the analysis, e.g. in the case of exploring and interacting with a protein on a 3D monitor and compatible interaction hardware. Moreover, in the past these approaches were limited to cost-intensive professional visualization facilities. The advent of new affordable, and often mobile technologies, provides high potential for using similar approaches on a regular basis for daily research. Visual Analytics is successfully being used for several years to analyze complex and heterogeneous datasets. Immersive Analytics combines these approaches now with new immersive and interactive technologies. This publication provides a short overview of related technologies, their history and Bioinformatics-related approaches. Six new applications on the path from VR to Immersive Analytics are being introduced and discussed.

}, keywords = {Computer Graphics, Imaging, Three-Dimensional, Molecular Conformation, Proteins, Software, User-Computer Interface, Virtual Reality}, issn = {1613-4516}, doi = {10.1515/jib-2018-0043}, author = {Sommer, Bj{\"o}rn and Marc Baaden and Krone, Michael and Woods, Andrew} } @article {2018|2045, title = {Hidden partners: Using cross-docking calculations to predict binding sites for proteins with multiple interactions}, journal = {Proteins: Structure, Function, and Bioinformatics}, volume = {00}, year = {2018}, pages = {1-15}, chapter = {1}, abstract = {

Abstract Protein-protein interactions control a large range of biological processes and their identification is essential to understand the underlying biological mechanisms. To complement experimental approaches, in silico methods are available to investigate protein-protein interactions. Cross-docking methods, in particular, can be used to predict protein binding sites. However, proteins can interact with numerous partners and can present multiple binding sites on their surface, which may alter the binding site prediction quality. We evaluate the binding site predictions obtained using complete cross-docking simulations of 358 proteins with 2 different scoring schemes accounting for multiple binding sites. Despite overall good binding site prediction performances, 68 cases were still associated with very low prediction quality, presenting individual area under the specificity-sensitivity ROC curve (AUC) values below the random AUC threshold of 0.5, since cross-docking calculations can lead to the identification of alternate protein binding sites (that are different from the reference experimental sites). For the large majority of these proteins, we show that the predicted alternate binding sites correspond to interaction sites with hidden partners, that is, partners not included in the original cross-docking dataset. Among those new partners, we find proteins, but also nucleic acid molecules. Finally, for proteins with multiple binding sites on their surface, we investigated the structural determinants associated with the binding sites the most targeted by the docking partners.

}, keywords = {alternate partners, binding site predictions, docking, multiple binding sites, protein-protein interfaces}, doi = {10.1002/prot.25506}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/prot.25506}, author = {Nathalie Lagarde and Alessandra Carbone and S Sacquin-Mora} } @article {2018|2034, title = {Influence of electric field on the amyloid-β(29-42) peptides embedded in a membrane bilayer.}, journal = {J Chem Phys}, volume = {148}, year = {2018}, month = {2018 Jan 28}, pages = {045105}, abstract = {

Alzheimer\&$\#$39;s disease is linked to various types of aggregates of amyloid-β (Aβ) peptide and their interactions with protein receptors and neuronal cell membranes. Little is known on the impact of the electric field on membrane-embedded Aβ. Here we use atomistic molecular dynamics simulations to study the effects of a constant electric field on the conformations of Aβdimer inside a membrane, where the electric field has a strength of 20 mV/nm which exists across the membrane of a human neuron. Starting from α-helix peptides, the transmembrane electric field (TMEF) accelerates the conversion from the Gly-out substate to the Gly-side and Gly-in substates. Starting from β-sheet peptides, TMEF induces changes of the kink and tilt angles at Gly33 and Gly37. Overall, in the simulations totaling 10 μs, TMEF establishes new ground states for the dimer, similar to induced-fit in ligand binding. Our findings indicate that TMEF can stabilize rare conformations of amyloid peptides, and this could influence the cleavage of the amyloid precursor protein and the formation of β-sheet oligomers in membrane bilayers.

}, issn = {1089-7690}, doi = {10.1063/1.5018459}, author = {Lu, Yan and Shi, Xiao-Feng and Salsbury, Freddie R and Philippe Derreumaux} } @article {2018|2087, title = {The major β-catenin/E-cadherin junctional binding site is a primary molecular mechano-transductor of differentiation .}, journal = {Elife}, volume = {7}, year = {2018}, month = {2018 07 19}, abstract = {

, the primary molecular mechanotransductive events mechanically initiating cell differentiation remain unknown. Here we find the molecular stretching of the highly conserved Y654-β-catenin-D665-E-cadherin binding site as mechanically induced by tissue strain. It triggers the increase of accessibility of the Y654 site, target of the Src42A kinase phosphorylation leading to irreversible unbinding. Molecular dynamics simulations of the β-catenin/E-cadherin complex under a force mimicking a 6 pN physiological mechanical strain predict a local 45\% stretching between the two α-helices linked by the site and a 15\% increase in accessibility of the phosphorylation site. Both are quantitatively observed using FRET lifetime imaging and non-phospho Y654 specific antibody labelling, in response to the mechanical strains developed by endogenous and magnetically mimicked early mesoderm invagination of gastrulating embryos. This is followed by the predicted release of 16\% of β-catenin from junctions, observed in FRAP, which initiates the mechanical activation of the β-catenin pathway process.

}, keywords = {Amino Acid Sequence, Animals, Armadillo Domain Proteins, Binding Sites, Cadherins, Cell Differentiation, Drosophila melanogaster, Drosophila Proteins, Fluorescence Resonance Energy Transfer, Mechanotransduction, Cellular, Molecular Dynamics Simulation, Phosphorylation, Protein Binding, Protein Conformation, Proto-Oncogene Proteins pp60(c-src), Sequence Homology, Transcription Factors}, issn = {2050-084X}, doi = {10.7554/eLife.33381}, author = {R{\"o}per, Jens-Christian and Mitrossilis, D{\'e}mosth{\`e}ne and Guillaume Stirnemann and Waharte, Fran{\c c}ois and Brito, Isabel and Fernandez-Sanchez, Maria-Elena and Marc Baaden and Salamero, Jean and Farge, Emmanuel} } @article {2018|2047, title = {Mechanical variations in proteins with large-scale motions highlight the formation of structural locks}, journal = {Journal of Structural Biology}, year = {2018}, keywords = {Coarse-grain simulations, Elastic network model, Protein domain motion, Proteins mechanics}, issn = {1047-8477}, doi = {https://doi.org/10.1016/j.jsb.2018.05.006}, url = {http://www.sciencedirect.com/science/article/pii/S1047847718301308}, author = {S Sacquin-Mora} } @article {2018|2044, title = {Meet-U: Educating through research immersion}, journal = {PLOS Computational Biology}, volume = {14}, year = {2018}, month = {03}, pages = {1-10}, abstract = {

We present a new educational initiative called Meet-U that aims to train students for collaborative work in computational biology and to bridge the gap between education and research. Meet-U mimics the setup of collaborative research projects and takes advantage of the most popular tools for collaborative work and of cloud computing. Students are grouped in teams of 4\–5 people and have to realize a project from A to Z that answers a challenging question in biology. Meet-U promotes \"coopetition,\" as the students collaborate within and across the teams and are also in competition with each other to develop the best final product. Meet-U fosters interactions between different actors of education and research through the organization of a meeting day, open to everyone, where the students present their work to a jury of researchers and jury members give research seminars. This very unique combination of education and research is strongly motivating for the students and provides a formidable opportunity for a scientific community to unite and increase its visibility. We report on our experience with Meet-U in two French universities with master\’s students in bioinformatics and modeling, with protein\–protein docking as the subject of the course. Meet-U is easy to implement and can be straightforwardly transferred to other fields and/or universities. All the information and data are available at www.meet-u.org.

}, doi = {10.1371/journal.pcbi.1005992}, url = {https://doi.org/10.1371/journal.pcbi.1005992}, author = {Abdollahi, Nika and Albani, Alexandre and Anthony, Eric and Baud, Agnes and Cardon, M{\'e}lissa and Clerc, Robert and Czernecki, Dariusz and Conte, Romain and David, Laurent and Delaune, Agathe and Djerroud, Samia and Fourgoux, Pauline and Guiglielmoni, Nad{\`e}ge and Laurentie, Jeanne and Lehmann, Nathalie and Lochard, Camille and Montagne, R{\'e}mi and Myrodia, Vasiliki and Opuu, Vaitea and Parey, Elise and Polit, L{\'e}lia and Priv{\'e}, Sylvain and Quignot, Chlo{\'e} and Ruiz-Cuevas, Maria and Sissoko, Mariam and Sompairac, Nicolas and Vallerix, Audrey and Verrecchia, Violaine and Delarue, Marc and Gu{\'e}rois, Raphael and Ponty, Yann and S Sacquin-Mora and Carbone, Alessandra and Froidevaux, Christine and Le Crom, St{\'e}phane and Lespinet, Olivier and Weigt, Martin and Abboud, Samer and Bernardes, Juliana and Bouvier, Guillaume and Dequeker, Chlo{\'e} and Ferr{\'e}, Arnaud and Fuchs, Patrick and Lelandais, Ga{\"e}lle and Poulain, Pierre and Richard, Hugues and Schweke, Hugo and Laine, Elodie and Lopes, Anne} } @inbook {2018|2084, title = {The modelling and enhancement of water hydrodynamics: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {273-285}, issn = {1364-5498}, doi = {10.1039/c8fd90021c}, author = {Marc Baaden and Borthakur, Manash Pratim and Casanova, Serena and Coalson, Rob and Freger, Viatcheslav and Gonzalez, Miguel and G{\'o}ra, Artur and Hinds, Bruce and Hirunpinyopas, Wisit and Hummer, Gerhard and Kumar, Manish and Lynch, Charlotte and Murail, Samuel and Noy, Aleksandr and Sansom, Mark and Song, Qilei and Vashisth, Harish and V{\"o}gele, Martin} } @article {2018|2035, title = {Molecular Mechanism of Protein Unfolding under Shear: A Lattice Boltzmann Molecular Dynamics Study.}, journal = {J Phys Chem B}, volume = {122}, year = {2018}, month = {2018 Feb 08}, pages = {1573-1579}, abstract = {

Proteins are marginally stable soft-matter entities that can be disrupted using a variety of perturbative stresses, including thermal, chemical, or mechanical ones. Fluid under extreme flow conditions is a possible route to probe the weakness of biomolecules and collect information on the molecular cohesive interactions that secure their stability. Moreover, in many cases, physiological flow triggers the functional response of specialized proteins as occurring in blood coagulation or cell adhesion. We deploy the Lattice Boltzmann molecular dynamics technique based on the coarse-grained model for protein OPEP to study the mechanism of protein unfolding under Couette flow. Our simulations provide a clear view of how structural elements of the proteins are affected by shear, and for the simple study case, the β-hairpin, we exploited the analogy to pulling experiments to quantify the mechanical forces acting on the protein under shear.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b10796}, author = {Sterpone, Fabio and Philippe Derreumaux and Melchionna, Simone} } @article {2018|2092, title = {Oriented chiral water wires in artificial transmembrane channels.}, journal = {Sci Adv}, volume = {4}, year = {2018}, month = {2018 03}, pages = {eaao5603}, abstract = {

Aquaporins (AQPs) feature highly selective water transport through cell membranes, where the dipolar orientation of structured water wires spanning the AQP pore is of considerable importance for the selective translocation of water over ions. We recently discovered that water permeability through artificial water channels formed by stacked imidazole I-quartet superstructures increases when the channel water molecules are highly organized. Correlating water structure with molecular transport is essential for understanding the underlying mechanisms of (fast) water translocation and channel selectivity. Chirality adds another factor enabling unique dipolar oriented water structures. We show that water molecules exhibit a dipolar oriented wire structure within chiral I-quartet water channels both in the solid state and embedded in supported lipid bilayer membranes (SLBs). X-ray single-crystal structures show that crystallographic water wires exhibit dipolar orientation, which is unique for chiral I-quartets. The integration of I-quartets into SLBs was monitored with a quartz crystal microbalance with dissipation, quantizing the amount of channel water molecules. Nonlinear sum-frequency generation vibrational spectroscopy demonstrates the first experimental observation of dipolar oriented water structures within artificial water channels inserted in bilayer membranes. Confirmation of the ordered confined water is obtained via molecular simulations, which provide quantitative measures of hydrogen bond strength, connectivity, and the stability of their dipolar alignment in a membrane environment. Together, uncovering the interplay between the dipolar aligned water structure and water transport through the self-assembled I-quartets is critical to understanding the behavior of natural membrane channels and will accelerate the systematic discovery for developing artificial water channels for water desalting.

}, issn = {2375-2548}, doi = {10.1126/sciadv.aao5603}, author = {Kocsis, Istvan and Sorci, Mirco and Vanselous, Heather and Murail, Samuel and Sanders, Stephanie E and Licsandru, Erol and Legrand, Yves-Marie and van der Lee, Arie and Marc Baaden and Petersen, Poul B and Belfort, Georges and Barboiu, Mihail} } @article {2018|2129, title = {Probing the quality control mechanism of the twin-arginine translocase with folding variants of a -designed heme protein.}, journal = {J Biol Chem}, volume = {293}, year = {2018}, month = {2018 05 04}, pages = {6672-6681}, abstract = {

Protein transport across the cytoplasmic membrane of bacterial cells is mediated by either the general secretion (Sec) system or the twin-arginine translocase (Tat). The Tat machinery exports folded and cofactor-containing proteins from the cytoplasm to the periplasm by using the transmembrane proton motive force as a source of energy. The Tat apparatus apparently senses the folded state of its protein substrates, a quality-control mechanism that prevents premature export of nascent unfolded or misfolded polypeptides, but its mechanistic basis has not yet been determined. Here, we investigated the innate ability of the model Tat system to recognize and translocate -designed protein substrates with experimentally determined differences in the extent of folding. Water-soluble, four-helix bundle maquette proteins were engineered to bind two, one, or no heme cofactors, resulting in a concomitant reduction in the extent of their folding, assessed with temperature-dependent CD spectroscopy and one-dimensional H NMR spectroscopy. Fusion of the archetypal N-terminal Tat signal peptide of the trimethylamine--oxide (TMAO) reductase (TorA) to the N terminus of the protein maquettes was sufficient for the Tat system to recognize them as substrates. The clear correlation between the level of Tat-dependent export and the degree of heme -induced folding of the maquette protein suggested that the membrane-bound Tat machinery can sense the extent of folding and conformational flexibility of its substrates. We propose that these artificial proteins are ideal substrates for future investigations of the Tat system\&$\#$39;s quality-control mechanism.

}, keywords = {Amino Acid Sequence, Bacterial Proteins, Circular Dichroism, Escherichia coli, Escherichia coli Proteins, Heme-Binding Proteins, Hemeproteins, Membrane Transport Proteins, Methylamines, Models, Molecular, Oxidoreductases, N-Demethylating, Periplasm, Protein Folding, Protein Sorting Signals, Protein Stability, Protein Transport, Proton Magnetic Resonance Spectroscopy, Substrate Specificity, Temperature}, issn = {1083-351X}, doi = {10.1074/jbc.RA117.000880}, author = {Sutherland, George A and Grayson, Katie J and Adams, Nathan B P and Mermans, Daphne M J and Jones, Alexander S and Robertson, Angus J and Auman, Dirk B and Brindley, Amanda A and Sterpone, Fabio and Tuffery, Pierre and Philippe Derreumaux and Dutton, P Leslie and Robinson, Colin and Hitchcock, Andrew and Hunter, C Neil} } @article {2018|2135, title = {Segmentation and the Entropic Elasticity of Modular Proteins}, journal = {J Phys Chem Lett}, volume = {9}, year = {2018}, month = {Aug}, pages = {4707-4713}, abstract = {

Single-molecule force spectroscopy utilizes polyproteins, which are composed of tandem modular domains, to study their mechanical and structural properties. Under the application of external load, the polyproteins respond by unfolding and refolding domains to acquire the most favored extensibility. However, unlike single-domain proteins, the sequential unfolding of the each domain modifies the free energy landscape (FEL) of the polyprotein nonlinearly. Here we use force-clamp (FC) spectroscopy to measure unfolding and collapse-refolding dynamics of polyubiquitin and poly(I91). Their reconstructed unfolding FEL involves hundreds of kB T in accumulating work performed against conformational entropy, which dwarfs the \∼30 kB T that is typically required to overcome the free energy difference of unfolding. We speculate that the additional entropic energy caused by segmentation of the polyprotein to individual proteins plays a crucial role in defining the \"shock absorber\" properties of elastic proteins such as the giant muscle protein titin.

}, doi = {10.1021/acs.jpclett.8b01925}, author = {Berkovich, Ronen and Fernandez, Vicente I and Guillaume Stirnemann and Valle-Orero, Jessica and Fernandez, Julio M} } @article {2018|2059, title = {A Streamlined, General Approach for Computing Ligand Binding Free Energies and Its Application to GPCR-Bound Cholesterol.}, journal = {Journal of Chemical Theory and Computation}, volume = {14}, year = {2018}, pages = {6560{\textendash}6573}, abstract = {

The theory of receptor-ligand binding equilibria has long been well-established in biochemistry, and was primarily constructed to describe dilute aqueous solutions. Accordingly, few computational approaches have been developed for making quantitative predictions of binding probabilities in environments other than dilute isotropic solution. Existing techniques, ranging from simple automated docking procedures to sophisticated thermodynamics-based methods, have been developed with soluble proteins in mind. Biologically and pharmacologically relevant protein-ligand interactions often occur in complex environments, including lamellar phases like membranes and crowded, nondilute solutions. Here, we revisit the theoretical bases of ligand binding equilibria, avoiding overly specific assumptions that are nearly always made when describing receptor-ligand binding. Building on this formalism, we extend the asymptotically exact Alchemical Free Energy Perturbation technique to quantifying occupancies of sites on proteins in a complex bulk, including phase-separated, anisotropic, or nondilute solutions, using a thermodynamically consistent and easily generalized approach that resolves several ambiguities of current frameworks. To incorporate the complex bulk without overcomplicating the overall thermodynamic cycle, we simplify the common approach for ligand restraints by using a single distance-from-bound-configuration (DBC) ligand restraint during AFEP decoupling from protein. DBC restraints should be generalizable to binding modes of most small molecules, even those with strong orientational dependence. We apply this approach to compute the likelihood that membrane cholesterol binds to known crystallographic sites on three GPCRs (β -adrenergic, 5HT-2B, and μ-opioid) at a range of concentrations. Nonideality of cholesterol in a binary cholesterol:phosphatidylcholine (POPC) bilayer is characterized and consistently incorporated into the interpretation. We find that the three sites exhibit very different affinities for cholesterol: The site on the adrenergic receptor is predicted to be high affinity, with 50\% occupancy for 1:10 CHOL:POPC mixtures. The sites on the 5HT-2B and μ-opioid receptor are predicted to be lower affinity, with 50\% occupancy for 1:10 CHOL:POPC and 1:10 CHOL:POPC, respectively. These results could not have been predicted from the crystal structures alone.

}, issn = {1549-9626}, doi = {10.1021/acs.jctc.8b00447}, author = {Salari, Reza and Joseph, Thomas and Lohia, Ruchi and J{\'e}r{\^o}me H{\'e}nin and Brannigan, Grace} } @inbook {2018|2083, title = {Structure and function of natural proteins for water transport: general discussion.}, booktitle = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {83-95}, keywords = {Molecular Structure, Proteins, Water}, issn = {1364-5498}, doi = {10.1039/c8fd90019a}, author = {Marc Baaden and Barboiu, Mihail and Bill, Roslyn M and Casanova, Serena and Chen, Chun-Long and Conner, Matthew and Freger, Viatcheslav and Gong, Bing and G{\'o}ra, Artur and Hinds, Bruce and Horner, Andreas and Hummer, Gerhard and Kumar, Manish and Lokesh, Mahesh and Mitra, Sushanta and Noy, Aleksandr and Pohl, Peter and Sadet, Aude and Sansom, Mark and T{\"o}rnroth-Horsefield, Susanna and Vashisth, Harish} } @article {2018|2138, title = {Three Weaknesses for Three Perturbations: Comparing Protein Unfolding Under Shear, Force, and Thermal Stresses}, journal = {J Phys Chem B}, volume = {122}, year = {2018}, month = {Dec}, pages = {11922-11930}, abstract = {

The perturbation of a protein conformation by a physiological fluid flow is crucial in various biological processes including blood clotting and bacterial adhesion to human tissues. Investigating such mechanisms by computer simulations is thus of great interest, but it requires development of ad hoc strategies to mimic the complex hydrodynamic interactions acting on the protein from the surrounding flow. In this study, we apply the Lattice Boltzmann Molecular Dynamics (LBMD) technique built on the implicit solvent coarse-grained model for protein Optimized Potential for Efficient peptide structure Prediction (OPEP) and a mesoscopic representation of the fluid solvent, to simulate the unfolding of a small globular cold-shock protein in shear flow and to compare it to the unfolding mechanisms caused either by mechanical or thermal perturbations. We show that each perturbation probes a specific weakness of the protein and causes the disruption of the native fold along different unfolding pathways. Notably, the shear flow and the thermal unfolding exhibit very similar pathways, while because of the directionality of the perturbation, the unfolding under force is quite different. For force and thermal disruption of the native state, the coarse-grained simulations are compared to all-atom simulations in explicit solvent, showing an excellent agreement in the explored unfolding mechanisms. These findings encourage the use of LBMD based on the OPEP model to investigate how a flow can affect the function of larger proteins, for example, in catch-bond systems.

}, doi = {10.1021/acs.jpcb.8b08711}, author = {Languin-Catto{\"e}n, Olivier and Melchionna, Simone and Philippe Derreumaux and Guillaume Stirnemann and Sterpone, Fabio} } @article {2018|2133, title = {Water dynamics in concentrated electrolytes: Local ion effect on hydrogen-bond jumps rather than collective coupling to ion clusters}, journal = {Proc Natl Acad Sci U S A}, volume = {115}, year = {2018}, month = {05}, pages = {E4953-E4954}, doi = {10.1073/pnas.1803988115}, author = {Guillaume Stirnemann and Jungwirth, Pavel and Laage, Damien} } @article {2018|2090, title = {Water permeation across artificial I-quartet membrane channels: from structure to disorder.}, journal = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {125-148}, abstract = {

Artificial water channels (AWCs) have been designed for water transport across membranes with the aim to mimic the high water permeability observed for biological systems such as aquaporins (\∼108-109 water molecules per s per channel), as well as their selectivity to reject ion permeation at the same time. Recent works on designed self-assembling alkylureido-ethylimidazole compounds forming imidazole-quartet channels (I-quartets), have shown both high water permeability and total ionic-rejection. I-quartets are thus promising candidates for further development of AWCs. However, the molecular mechanism of water permeation as well as I-quartet organization and stability in a membrane environment need to be fully understood to guide their optimal design. Here, we use a wide range of all-atom molecular dynamics (MD) simulations and their analysis to understand the structure/activity relationships of the I-quartet channels. Four different types with varying alkyl chain length or chirality have been studied in a complex fully hydrated lipid bilayer environment at both microsecond and nanosecond scale. Microsecond simulations show two distinct behaviors; (i) two out of four systems maintain chiral dipolar oriented water wires, but also undergo a strong reorganization of the crystal shape, (ii) the two other I-quartet channels completely lose the initial organization, nonetheless keeping a water transport activity. Short MD simulations with higher time resolution were conducted to characterize the dynamic properties of water molecules in these model channels and provided a detailed hypothesis on the molecular mechanism of water permeation. The ordered confined water was characterized with quantitative measures of hydrogen-bond life-time and single particle dynamics, showing variability among I-quartet channels. We will further discuss the underlying assumptions, currently based on self-aggregation simulations and crystal patches embedded in lipid bilayer simulations and attempt to describe possible alternative approaches to computationally capture the water permeation mechanism and the self-assembly process of these AWCs.

}, issn = {1364-5498}, doi = {10.1039/c8fd00046h}, author = {Murail, Samuel and Vasiliu, Tudor and Neamtu, Andrei and Barboiu, Mihail and Sterpone, Fabio and Marc Baaden} } @article {2017|2024, title = {Ab Initio Simulations of Water Dynamics in Aqueous TMAO Solutions: Temperature and Concentration Effects}, journal = {J Phys Chem B}, year = {2017}, month = {Dec}, abstract = {

We use ab initio molecular dynamics simulation to study the effect of hydrophobic groups on the dynamics of water molecules in aqueous solutions of trimethylamine N-oxide (TMAO). We show that hydrophobic groups induce a moderate (\<2-fold) slowdown of water reorientation and hydrogen-bond dynamics in dilute solutions, but that this slowdown rapidly increases with solute concentration. In addition, the slowdown factor is found to vary very little with temperature, thus suggesting an entropic origin. All of these results are in quantitative agreement with prior classical molecular dynamics simulations and with the previously suggested excluded-volume model. The hydrophilic TMAO headgroup is found to affect water dynamics more strongly than the hydrophobic moiety, and the magnitude of this slowdown is very sensitive to the strength of the water-solute hydrogen-bond.

}, doi = {10.1021/acs.jpcb.7b09989}, author = {Guillaume Stirnemann and Elise Dubou{\'e}-Dijon and Laage, Damien} } @article {2017|2033, title = {Configurational Disorder of Water Hydrogen Bond Network at the Protein Dynamical Transition}, volume = {121}, year = {2017}, pages = {6792-6798}, author = {O. Rahaman and M. Kalimeri and M. Katava and A. Paciaroni and F. Sterpone} } @article {2017|2025, title = {Critical structural fluctuations of proteins upon thermal unfolding challenge the Lindemann criterion}, journal = {Proc Natl Acad Sci U S A}, volume = {114}, year = {2017}, month = {Aug}, pages = {9361-9366}, abstract = {

Internal subnanosecond timescale motions are key for the function of proteins, and are coupled to the surrounding solvent environment. These fast fluctuations guide protein conformational changes, yet their role for protein stability, and for unfolding, remains elusive. Here, in analogy with the Lindemann criterion for the melting of solids, we demonstrate a common scaling of structural fluctuations of lysozyme protein embedded in different environments as the thermal unfolding transition is approached. By combining elastic incoherent neutron scattering and advanced molecular simulations, we show that, although different solvents modify the protein melting temperature, a unique dynamical regime is attained in proximity of thermal unfolding in all solvents that we tested. This solvation shell-independent dynamical regime arises from an equivalent sampling of the energy landscape at the respective melting temperatures. Thus, we propose that a threshold for the conformational entropy provided by structural fluctuations of proteins exists, beyond which thermal unfolding is triggered.

}, keywords = {cell thermal stability, Lindemann criterion, Molecular Dynamics Simulation, neutron scattering, protein dynamics}, doi = {10.1073/pnas.1707357114}, author = {Katava, Marina and Guillaume Stirnemann and Zanatta, Marco and Capaccioli, Simone and Pachetti, Maria and Ngai, K L and Sterpone, Fabio and Paciaroni, Alessandro} } @article {2017|2020, title = {Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {May}, pages = {1858}, author = {Colloc{\textquoteright}h, N. and S Sacquin-Mora and Avella, G. and Dhaussy, A. C. and Prange, T. and Vallone, B. and Girard, E.} } @article {2017|2023, title = {Mechanics of Protein Adaptation to High Temperatures}, journal = {J Phys Chem Lett}, volume = {8}, year = {2017}, month = {Dec}, pages = {5884-5890}, abstract = {

Inspired by Somero\&$\#$39;s corresponding state principle that relates protein enhanced thermal stability with mechanical rigidity, we deployed state of the art computational techniques (based on atomistic steered molecular dynamics and Hamiltonian-replica exchange simulations) to study the in silico realization of mechanical and thermal unfolding of two homologous Csp proteins that have evolved to thrive in different thermal environments. By complementing recent single-molecule experiments, we unambiguously show that, for these homologues whose structures are very similar, the increased thermal resistance of the thermophilic variant is not associated with an increased mechanical stability. Our approach provides microscopic insights that are otherwise inaccessible to experimental techniques, and explains why the protein weak spots for thermal and mechanical denaturation are distinct.

}, doi = {10.1021/acs.jpclett.7b02611}, author = {Guillaume Stirnemann and Sterpone, Fabio} } @article {2017, title = {Mobility and core-protein binding patterns of disordered C-terminal tails in β-tubulin isotypes.}, journal = {Biochemistry}, volume = { 56}, year = {2017}, pages = {1746{\textendash}1756}, chapter = {1746}, abstract = {

Although they play a significant part in the regulation of microtubule structure, dynamics and function, the disordered C-terminal tails of tubulin remain invisible to experimental structural methods and do not appear in the crystallographic structures that are currently available in the Protein Data Bank. Interestingly, these tails concentrate most of the sequence variability between tubulin isotypes, and are the sites of the principal post-translational modifications undergone by this protein. Using homology modeling, we developed two complete models for the human αI/βI and αI/βIII tubulin isotypes that include their C-terminal tails. We then investigated the conformational variability of the two β-tails using long time-scale classical Molecular Dynamics (MD) simulations that revealed similar features, notably the unexpected presence of common anchoring regions on the surface of the tubulin dimer, but also distinctive mobility or interaction patterns, some of which could be related to the tail lengths and charge distributions. We also observed in our simulations that the C-terminal tail from the βI isotype, but not the βIII, formed contacts in the putative binding site of a recently discovered peptide that disrupts microtubule formation in glioma cells. Hindering the binding site in the βI isotype would be consistent with this peptide\’s preferential disruption of microtubule formation in glioma, whose cells overexpress βIII, compared to normal glial cells. While these observations need to be confirmed with more intensive sampling, our study opens up new perspectives for the development of isotype-specific chemotherapy drugs.

}, doi = {10.1021/acs.biochem.6b00988}, author = {Laurin, Yoann and Eyer, Joel and Charles H. Robert and Chantal Pr{\'e}vost and S Sacquin-Mora} } @conference {2017|2101, title = {Molecular Visualization of Computational Biology Data: A Survey of Surveys}, booktitle = {EuroVis 2017 - Short Papers}, year = {2017}, publisher = {The Eurographics Association}, organization = {The Eurographics Association}, isbn = {978-3-03868-043-7}, doi = {10.2312/eurovisshort.20171146}, author = {Alharbi, Naif and Alharbi, Mohammad and Martinez, Xavier and Krone, Michael and Rose, Alexander S. and Marc Baaden and Laramee, Robert S. and Chavent, Matthieu}, editor = {Barbora Kozlikova and Tobias Schreck and Thomas Wischgoll} } @article {2017|2037, title = {Multifunctional energy landscape for a DNA G-quadruplex: An evolved molecular switch.}, journal = {J Chem Phys}, volume = {147}, year = {2017}, month = {2017 Oct 21}, pages = {152715}, abstract = {

We explore the energy landscape for a four-fold telomere repeat, obtaining interconversion pathways between six experimentally characterised G-quadruplex topologies. The results reveal a multi-funnel system, with a variety of intermediate configurations and misfolded states. This organisation is identified with the intrinsically multi-functional nature of the system, suggesting a new paradigm for the classification of such biomolecules and clarifying issues regarding apparently conflicting experimental results.

}, issn = {1089-7690}, doi = {10.1063/1.4997377}, author = {Cragnolini, Tristan and Chakraborty, Debayan and Sponer, Jiri and Philippe Derreumaux and Pasquali, Samuela and Wales, David J} } @article {2017|2029, title = {Multi-scale simulations of biological systems using the OPEP coarse-grained model.}, journal = {Biochem Biophys Res Commun}, year = {2017}, month = {2017 Sep 14}, abstract = {

Biomolecules are complex machines that are optimized by evolution to properly fulfill or contribute to a variety of biochemical tasks in the cellular environment. Computer simulations based on quantum mechanics and atomistic force fields have been proven to be a powerful microscope for obtaining valuable insights into many biological, physical, and chemical processes. Many interesting phenomena involve, however, a time scale and a number of degrees of freedom, notably if crowding is considered, that cannot be explored at an atomistic resolution. To bridge the gap between reality and simulation, many different advanced computational techniques and coarse-grained (CG) models have been developed. Here, we report some applications of the CG OPEP protein model to amyloid fibril formation, the response of catch-bond proteins to two types of fluid flow, and interactive simulations to fold peptides with well-defined 3D structures or with intrinsic disorder.

}, issn = {1090-2104}, doi = {10.1016/j.bbrc.2017.08.165}, author = {Sterpone, Fabio and Doutreligne, S{\'e}bastien and Tran, Thanh Thuy and Melchionna, Simone and Marc Baaden and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2017|2040, title = {Small static electric field strength promotes aggregation-prone structures in amyloid-β(29-42).}, journal = {J Chem Phys}, volume = {146}, year = {2017}, month = {2017 Apr 14}, pages = {145101}, abstract = {

The formation of senile plaques in central neural system resulting from the aggregation of the amyloid β (Aβ) of 40 and 42 residues is one of the two hallmarks of Alzheimer\&$\#$39;s disease. Numerous experiments and computational studies have shown that the aggregation of Aβ peptides in vitro is very complex and depends on many factors such as pH, agitation, temperature, and peptide concentration. The impact of a static electric field (EF) on amyloid peptide aggregation has been much less studied, although EFs may have some applications to treat Parkinson\&$\#$39;s disease symptoms. Here, we study the influence of an EF strength of 20 mV/nm, present in the human brains, on the conformation of the Aβdimer. Our 7 μs non-equilibrium atomistic simulations in aqueous solution show that this field-strength promotes substantially the formation of β-hairpins, believed to be a very important intermediate state during aggregation. This work also suggests that structural biology experiments conducted under appropriate EF strengths may help reduce the conformational heterogeneity of Aβ/Aβdimers and provide significant insights into their structures that may be disease-causing.

}, issn = {1089-7690}, doi = {10.1063/1.4979866}, author = {Lu, Yan and Shi, Xiao-Feng and Salsbury, Freddie R and Philippe Derreumaux} } @article {2017|1686, title = {Smoothed biasing forces yield unbiased free energies with the extended-system Adaptive Biasing Force method}, journal = {J. Phys. Chem. B}, volume = {121}, year = {2017}, month = {dec}, pages = {3676{\textendash}3685}, doi = {10.1021/acs.jpcb.6b10055}, author = {Lesage, A. and Leli{\`e}vre, T. and Stoltz, G. and J{\'e}r{\^o}me H{\'e}nin} } @article {2017|2026, title = {Tailoring protein nanomechanics with chemical reactivity}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {Jun}, pages = {15658}, abstract = {

The nanomechanical properties of elastomeric proteins determine the elasticity of a variety of tissues. A widespread natural tactic to regulate protein extensibility lies in the presence of covalent disulfide bonds, which significantly enhance protein stiffness. The prevalent in vivo strategy to form disulfide bonds requires the presence of dedicated enzymes. Here we propose an alternative chemical route to promote non-enzymatic oxidative protein folding via disulfide isomerization based on naturally occurring small molecules. Using single-molecule force-clamp spectroscopy, supported by DFT calculations and mass spectrometry measurements, we demonstrate that subtle changes in the chemical structure of a transient mixed-disulfide intermediate adduct between a protein cysteine and an attacking low molecular-weight thiol have a dramatic effect on the protein\&$\#$39;s mechanical stability. This approach provides a general tool to rationalize the dynamics of S-thiolation and its role in modulating protein nanomechanics, offering molecular insights on how chemical reactivity regulates protein elasticity.

}, doi = {10.1038/ncomms15658}, author = {Beedle, Amy E M and Mora, Marc and Lynham, Steven and Guillaume Stirnemann and Garcia-Manyes, Sergi} } @article {2017|2030, title = {Why Is Research on Amyloid-β Failing to Give New Drugs for Alzheimer{\textquoteright}s Disease?}, journal = {ACS Chem Neurosci}, volume = {8}, year = {2017}, month = {2017 Jul 19}, pages = {1435-1437}, abstract = {

The two hallmarks of Alzheimer\&$\#$39;s disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure.

}, keywords = {Alzheimer Disease, Amyloid beta-Peptides, Animals, Drug Discovery, Humans, Neuroprotective Agents}, issn = {1948-7193}, doi = {10.1021/acschemneuro.7b00188}, author = {Doig, Andrew J and Del Castillo-Frias, Maria P and Berthoumieu, Olivia and Tarus, Bogdan and Nasica-Labouze, Jessica and Sterpone, Fabio and Phuong Hoang Nguyen and Hooper, Nigel M and Faller, Peter and Philippe Derreumaux} } @inbook {2016|1721, title = {Bridging Enzymatic Structure Function via Mechanics: A Coarse-Grain Approach}, booktitle = {Methods in Enzymology}, year = {2016}, pages = {227{\textendash}248}, publisher = {Academic Press}, organization = {Academic Press}, keywords = {Coarse-grain simulations}, issn = {0076-6879}, doi = {10.1016/bs.mie.2016.05.022}, url = {http://www.sciencedirect.com/science/article/pii/S007668791630057X}, author = {S Sacquin-Mora} } @article {2016|1656, title = {Coarse-grained and All-atom Simulations towards the Early and Late Steps of Amyloid Fibril Formation}, journal = {Isr. J. Chem.}, volume = {DOI: 10.1002/ijch.201600048.}, year = {2016}, author = {M. Chiricotto and Thanh-Thuy Tran and Phuong Hoang Nguyen and S. Melchionna and Fabio Sterpone and Philippe Derreumaux} } @article {2016|1707, title = {Coarse-Grained Simulations Complemented by Atomistic Molecular Dynamics Provide New Insights into Folding and Unfolding of Human Telomeric G-Quadruplexes}, journal = {J. Chem. Theory Comput.}, volume = {12}, number = {12}, year = {2016}, month = {dec}, pages = {6077{\textendash}6097}, abstract = {G-quadruplexes are the most important non canonical DNA architectures. Many quadruplex-forming sequences, including the human telomeric sequence d(GGGTTA)(n), have been investigated due to their implications in cancer and other diseases, and because of their potential in DNA-based nanotechnology. Despite the availability of atomistic structural studies of folded G-quadruplexes, their folding pathways remain mysterious, and mutually contradictory models of folding coexist in the literature. Recent experiments convincingly demonstrated that G-quadruplex folding often takes days to reach thermodynamic equilibrium. Based on atomistic simulations of diverse classes of intermediates in G-quadruplex folding, we have suggested that the folding is an extremely multipathway process combining a kinetic partitioning mechanism with conformational diffusion. However, complete G-quadruplex folding is far beyond the time scale of atomistic simulations. Here we use high-resolution coarse-grained simulations to investigate potential unfolding intermediates, whose structural dynamics are then further explored with all-atom simulations. This multiscale approach indicates how various pathways are interconnected in a complex network. Spontaneous conversions between different folds are observed. We demonstrate the inability of simple order parameters, such as radius of gyration or the number of native H-bonds, to describe the folding landscape of the G-quadruplexes. Our study also provides information relevant to further development of the coarse grained force field.}, issn = {1549-9618}, doi = {10.1021/acs.jctc.6b00667}, author = {Stadlbauer, Petr and Mazzanti, Liuba and Cragnolini, Tristan and Wales, David J. and Philippe Derreumaux and Pasquali, Samuela and Sponer, Jiri} } @article {2016|1712, title = {Dimerization Mechanism of Alzheimer A beta(40) Peptides: The High Content of Intrapeptide-Stabilized Conformations in A2V and A2T Heterozygous Dimers Retards Amyloid Fibril Formation}, journal = {J. Phys. Chem. B}, volume = {120}, number = {47}, year = {2016}, pages = {12111{\textendash}12126}, abstract = {Amyloid beta (A beta) oligomerization is associated with the origin and progression of Alzheimer{\textquoteright}s disease (AD). While the A2V mutation enhances aggregation kinetics and toxicity, mixtures of wild-type (WT) and A2V, and also WT and A2T, peptides retard fibril formation and protect against AD. In this study, we simulate the equilibrium ensemble of WT:A2T A beta(40) dimer by means of extensive atomistic replica exchange molecular dynamics and compare our results with previous equivalent simulations of A2V:A2V, WT:WT, and WT:A2V A beta(40) dimers for a total time scale of nearly 0.1 ms. Qualitative comparison of the resulting thermodynamic properties, such as the relative binding free energies, with the reported experimental kinetic and thermodynamic data affords us important insight into the conversion from slow-pathway to fast-pathway dimer conformations. The crucial reaction coordinate or driving force of such transformation turns out to be related to hydrophobic interpeptide interactions. Analysis of the equilibrium ensembles shows that the fast-pathway conformations contain interpeptide out-of-register antiparallel beta-sheet structures at short interpeptide distances. In contrast, the slow-pathway conformations are formed by the association of peptides at large interpeptide distances and high intrapeptide compactness, such as conformations containing intramolecular three-stranded beta-sheets which sharply distinguish fast (A2V:A2V and WT:WT) and slow (WT:A2T and WT:A2V) amyloid-forming sequences. Also, this analysis leads us to predict that a molecule stabilizing the intramolecular three-stranded beta-sheet or inhibiting the formation of an interpeptide beta-sheet spanning residues 17-20 and 31-37 would further reduce fibril formation and probably the cytotoxicity of A beta species.}, issn = {1520-6106}, doi = {10.1021/acs.jpcp.6b10722}, author = {Phuong Hoang Nguyen and Fabio Sterpone and Pouplana, Ramon and Philippe Derreumaux and Campanera, Josep M.} } @article {2016|1630, title = {Evaluation of the coarse-grained OPEP force field for protein-protein docking}, journal = {Bmc Biophysics}, volume = {9}, year = {2016}, month = {apr}, abstract = {Background: Knowing the binding site of protein-protein complexes helps understand their function and shows possible regulation sites. The ultimate goal of protein-protein docking is the prediction of the three-dimensional structure of a protein-protein complex. Docking itself only produces plausible candidate structures, which must be ranked using scoring functions to identify the structures that are most likely to occur in nature. Methods: In this work, we rescore rigid body protein-protein predictions using the optimized potential for efficient structure prediction (OPEP), which is a coarse-grained force field. Using a force field based on continuous functions rather than a grid-based scoring function allows the introduction of protein flexibility during the docking procedure. First, we produce protein-protein predictions using ZDOCK, and after energy minimization via OPEP we rank them using an OPEP-based soft rescoring function. We also train the rescoring function for different complex classes and demonstrate its improved performance for an independent dataset. Results: The trained rescoring function produces a better ranking than ZDOCK for more than 50 \% of targets, rising to over 70 \% when considering only enzyme/inhibitor complexes. Conclusions: This study demonstrates for the first time that energy functions derived from the coarse-grained OPEP force field can be employed to rescore predictions for protein-protein complexes.}, issn = {2046-1682}, doi = {10.1186/s13628-016-0029-y}, author = {Kynast, Philipp and Philippe Derreumaux and Strodel, Birgit} } @article {2016|1759, title = {Great interactions: How binding incorrect partners can teach us about protein recognition and function}, journal = {Proteins: Struct., Funct., Bioinf.}, year = {2016}, pages = {n/a-n/a}, keywords = {binding sites prediction, coarse grain models, docking, protein-protein interaction, protein-protein interfaces}, issn = {1097-0134}, doi = {10.1002/prot.25086}, author = {Vamparys, Lydie and B. Laurent and Carbone, A. and S Sacquin-Mora} } @conference {2016|1607, title = {Hydrodynamic Effects on Amyloid-beta Aggregation}, booktitle = {Biophys. J.}, volume = {110}, number = {3, 1}, year = {2016}, note = {60th Annual Meeting of the Biophysical-Society, Los Angeles, CA, FEB 27-MAR 02, 2016}, month = {feb}, pages = {219A}, publisher = {Biophys Soc}, organization = {Biophys Soc}, issn = {0006-3495}, author = {Chiricotto, Mara and Melchionna, Simone and Philippe Derreumaux and Fabio Sterpone} } @article {2016|1702, title = {Hydrodynamic effects on beta-amyloid (16-22) peptide aggregation}, journal = {J. Chem. Phys.}, volume = {145}, number = {3}, year = {2016}, month = {jul}, abstract = {Computer simulations based on simplified representations are routinely used to explore the early steps of amyloid aggregation. However, when protein models with implicit solvent are employed, these simulations miss the effect of solvent induced correlations on the aggregation kinetics and lifetimes of metastable states. In this work, we apply the multi-scale Lattice Boltzmann Molecular Dynamics technique (LBMD) to investigate the initial aggregation phases of the amyloid A beta(16-22) peptide. LBMD includes naturally hydrodynamic interactions (HIs) via a kinetic on-lattice representation of the fluid kinetics. The peptides are represented by the flexible OPEP coarse-grained force field. First, we have tuned the essential parameters that control the coupling between the molecular and fluid evolutions in order to reproduce the experimental diffusivity of elementary species. The method is then deployed to investigate the effect of HIs on the aggregation of 100 and 1000 A beta(16-22) peptides. We show that HIs clearly impact the aggregation process and the fluctuations of the oligomer sizes by favouring the fusion and exchange dynamics of oligomers between aggregates. HIs also guide the growth of the leading largest cluster. For the 100 A beta(16-22) peptide system, the simulation of similar to 300 ns allowed us to observe the transition from ellipsoidal assemblies to an elongated and slightly twisted aggregate involving almost the totality of the peptides. For the 1000 A beta(16-22) peptides, a system of unprecedented size at quasi-atomistic resolution, we were able to explore a branched disordered fibril-like structure that has never been described by other computer simulations, but has been observed experimentally. Published by AIP Publishing.}, issn = {0021-9606}, doi = {10.1063/1.4958323}, author = {Chiricotto, Mara and Melchionna, Simone and Philippe Derreumaux and Fabio Sterpone} } @article {2016|1578, title = {Impact of the A2V Mutation on the Heterozygous and Homozygous A beta 1-40 Dimer Structures from Atomistic Simulations}, journal = {Acs Chem. Neurosci.}, volume = {7}, number = {6}, year = {2016}, month = {jun}, pages = {823{\textendash}832}, abstract = {The A2V mutation was reported to protect from Alzheimer{\textquoteright}s disease in its heterozygous form and cause an early Alzheimer{\textquoteright}s disease type dementia in its homozygous form. Experiments showed that the aggregation rate follows the order A2V > WT (wild-type) > A2V-WT. To understand the impact of this mutation, we carried out replica exchange molecular dynamics simulations of A beta 1-40 WT-A2V and A2V-A2V dimers and compared to the WT dimer. Our atomistic simulations reveal that the mean secondary structure remains constant, but there are substantial differences in the intramolecular and intermolecular conformations upon single and double A2V mutation. Upon single mutation, the intrinsic disorder is reduced, the intermolecular potential energies are reduced, the population of intramolecular three-stranded beta-sheets is increased, and the number of all a dimer topologies is decreased. Taken together, these results offer an explanation for the reduced aggregation rate of the A beta 1-40 A2V-WT peptides and the protective effect of A2V in heterozygotes.}, issn = {1948-7193}, doi = {10.1021/acschemneuro.6b00053}, author = {Phuong Hoang Nguyen and Fabio Sterpone and Campanera, Josep M. and Nasica-Labouze, Jessica and Philippe Derreumaux} } @article {2016|1639, title = {MP2 and DFT studies of beta-D-neocarrabiose and beta-D-neocarrabiose monohydrate}, journal = {Comput. Theor. Chem.}, volume = {1091}, year = {2016}, month = {sep}, pages = {24{\textendash}30}, abstract = {MP2 and density functional theory calculations have been carried out on beta-D-neocarrabiose and its mono hydrate in order to determine the conformational preferences of these molecules in the gas phase and in solvent. Relaxed iso-energetic maps were first obtained using B3LYP/6-31G(d). Then, the lower energy conformers were further fully optimized using B3LYP, B3PW91 and MP2 methods. Overall, it was demonstrated that a lower energy conformer corresponding to the couple of dihedral angles (Phi,Psi)= (69 degrees,-117 degrees) is detected either in the gas phase or in solvent provided that full optimizations are performed on the conformers corresponding to the minima detected from the iso-energetic maps. (C) 2016 Elsevier B.V. All rights reserved.}, issn = {2210-271X}, doi = {10.1016/j.comptc.2016.07.009}, author = {Bestaoui-Berrekhchi-Berrahma, N. and Sekkal-Rahal, M. and Philippe Derreumaux and Yousfi, N.} } @article {2016|1735, title = {Multiscale simulation of molecular processes in cellular environments}, journal = {Philosophical Transactions of the Royal Society A-mathematical Physical and Engineering Sciences}, volume = {374}, number = {2080}, year = {2016}, abstract = {We describe the recent advances in studying biological systems via multiscale simulations. Our scheme is based on a coarse-grained representation of the macromolecules and a mesoscopic description of the solvent. The dual technique handles particles, the aqueous solvent and their mutual exchange of forces resulting in a stable and accurate methodology allowing biosystems of unprecedented size to be simulated. This article is part of the themed issue {\textquoteleft}Multiscale modelling at the physics-chemistry-biology interface{\textquoteright}.}, issn = {1364-503X}, doi = {10.1098/rsta.2016.0225}, author = {Chiricotto, Mara and Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {2016|1672, title = {A Novel Bifunctional Alkylphenol Anesthetic Allows Characterization of gamma-Aminobutyric Acid, Type A (GABAA), Receptor Subunit Binding Selectivity in Synaptosomes.}, journal = {J. Biol. Chem}, volume = {291}, year = {2016}, month = {sep}, pages = {20473{\textendash}86}, abstract = {

Propofol, an intravenous anesthetic, is a positive modulator of the GABAA receptor, but the mechanistic details, including the relevant binding sites and alternative targets, remain disputed. Here we undertook an in-depth study of alkylphenol-based anesthetic binding to synaptic membranes. We designed, synthesized, and characterized a chemically active alkylphenol anesthetic (2-((prop-2-yn-1-yloxy)methyl)-5-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenol, AziPm-click (1)), for affinity-based protein profiling (ABPP) of propofol-binding proteins in their native state within mouse synaptosomes. The ABPP strategy captured approximately 4\% of the synaptosomal proteome, including the unbiased capture of five alpha or beta GABAA receptor subunits. Lack of gamma2 subunit capture was not due to low abundance. Consistent with this, independent molecular dynamics simulations with alchemical free energy perturbation calculations predicted selective propofol binding to interfacial sites, with higher affinities for alpha/beta than gamma-containing interfaces. The simulations indicated hydrogen bonding is a key component leading to propofol-selective binding within GABAA receptor subunit interfaces, with stable hydrogen bonds observed between propofol and alpha/beta cavity residues but not gamma cavity residues. We confirmed this by introducing a hydrogen bond-null propofol analogue as a protecting ligand for targeted-ABPP and observed a lack of GABAA receptor subunit protection. This investigation demonstrates striking interfacial GABAA receptor subunit selectivity in the native milieu, suggesting that asymmetric occupancy of heteropentameric ion channels by alkylphenol-based anesthetics is sufficient to induce modulation of activity.

}, keywords = {anesthesia, anesthetic, click chemistry, GABA receptor, photoaffinity labeling}, doi = {10.1074/jbc.M116.736975}, author = {Woll, Kellie A. and Murlidaran, Sruthi and Pinch, Benika J. and J{\'e}r{\^o}me H{\'e}nin and Wang, Xiaoshi and Salari, Reza and Covarrubias, Manuel and Dailey, William P. and Grace Brannigan and Garcia, Benjamin A. and Roderic G Eckenhoff} } @article {2016|2027, title = {Orientational Dynamics of Water at an Extended Hydrophobic Interface}, journal = {J Am Chem Soc}, volume = {138}, year = {2016}, month = {May}, pages = {5551-60}, abstract = {

We report on the orientational dynamics of water at an extended hydrophobic interface with an octadecylsilane self-assembled monolayer on fused silica. The interfacial dangling OH stretch mode is excited with a resonant pump, and its evolution followed in time by a surface-specific, vibrationally resonant, infrared-visible sum-frequency probe. High sensitivity pump-probe anisotropy measurements and isotopic dilution clearly reveal that the decay of the dangling OH stretch excitation is almost entirely due to a jump to a hydrogen-bonded configuration that occurs in 1.61 $\pm$ 0.10 ps. This is more than twice as fast as the jump time from one hydrogen-bonded configuration to another in bulk H2O but about 50\% slower than the reported out-of-plane reorientation at the air/water interface. In contrast, the intrinsic population lifetime of the dangling OH stretch in the absence of such jumps is found to be \>10 ps. Molecular dynamics simulations of air/water and hexane/water interfaces reproduce the fast jump dynamics of interfacial dangling OH with calculated jump times of 1.4 and 1.7 ps for the air and hydrophobic interfaces, respectively. The simulations highlight that while the air/water and hydrophobic/water surfaces exhibit great structural similarities, a small stabilization of the OH groups by the hydrophobic interface produces the pronounced difference in the dynamics of dangling bonds.

}, doi = {10.1021/jacs.6b01820}, author = {Xiao, Shunhao and Figge, Florian and Guillaume Stirnemann and Laage, Damien and McGuire, John A} } @article {2016|1744, title = {Picosecond infrared laser-induced all-atom nonequilibrium molecular dynamics simulation of dissociation of viruses}, journal = {Phys. Chem. Chem. Phys.}, volume = {18}, number = {17}, year = {2016}, month = {may}, pages = {11951{\textendash}11958}, abstract = {Since the discovery of the plant pathogen tobacco mosaic virus as the first viral entity in the late 1800s, viruses traditionally have been mainly thought of as pathogens for disease-resistances. However, viruses have recently been exploited as nanoplatforms with applications in biomedicine and materials science. To this aim, a large majority of current methods and tools have been developed to improve the physical stability of viral particles, which may be critical to the extreme physical or chemical conditions that viruses may encounter during purification, fabrication processes, storage and use. However, considerably fewer studies are devoted to developing efficient methods to degrade or recycle such enhanced stability biomaterials. With this in mind, we carry out all-atom nonequilibriummolecular dynamics simulation, inspired by the recently developed mid-infrared free-electron laser pulse technology, to dissociate viruses. Adopting the poliovirus as a representative example, we find that the primary step in the dissociation process is due to the strong resonance between the amide I vibrational modes of the virus and the tuned laser frequencies. This process is determined by a balance between the formation and dissociation of the protein shell, reflecting the highly plasticity of the virus. Furthermore, our method should provide a feasible approach to simulate viruses, which is otherwise too expensive for conventional equilibrium all-atom simulations of such very large systems. Our work shows a proof of concept which may open a new, efficient way to cleave or to recycle virus-based materials, provide an extremely valuable tool for elucidating mechanical aspects of viruses, and may well play an important role in future fighting against virus-related diseases.}, issn = {1463-9076}, doi = {10.1039/c5cp07711g}, author = {Viet Hoang Man and Van-Oanh, Nguyen-Thi and Philippe Derreumaux and Li, Mai Suan and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2016|1447, title = {{S}alt-{E}xcluding {A}rtificial {W}ater {C}hannels {E}xhibiting {E}nhanced {D}ipolar {W}ater and {P}roton {T}ranslocation}, journal = {J. Am. Chem. Soc.}, volume = {138}, number = {16}, year = {2016}, month = {apr}, pages = {5403{\textendash}5409}, author = {Licsandru, E. and Kocsis, I. and Shen, Y. X. and Murail, S. and Legrand, Y. M. and van der Lee, A. and Tsai, D. and Marc Baaden and Kumar, M. and Barboiu, M.} } @article {2016|1550, title = {{S}ites of {A}nesthetic {I}nhibitory {A}ction on a {C}ationic {L}igand-{G}ated {I}on {C}hannel}, journal = {Structure}, volume = {24a}, number = {4}, year = {2016}, month = {apr}, pages = {595{\textendash}605}, author = {Laurent, B. and Murail, S. and Shahsavar, A. and Sauguet, L. and Delarue, M. and Marc Baaden} } @article {2016|1687, title = {Stability and Function at High Temperature. What Makes a Thermophilic GTPase Different from Its Mesophilic Homologue}, journal = {J. Phys. Chem. B}, volume = {120}, year = {2016}, pages = {2721{\textendash}2730}, abstract = {

Comparing homologous enzymes adapted to different thermal environments aids to shed light on their delicate stability/function trade-off. Protein mechanical rigidity was postulated to secure stability and high-temperature functionality of thermophilic proteins. In this work, we challenge the corresponding-state principle for a pair of homologous GTPase domains by performing extensive molecular dynamics simulations, applying conformational and kinetic clustering, as well as exploiting an enhanced sampling technique (REST2). While it was formerly shown that enhanced protein flexibility and high temperature stability can coexist in the apo hyperthermophilic variant, here we focus on the holo states of both homologues by mimicking the enzymatic turnover. We clearly show that the presence of the ligands affects the conformational landscape visited by the proteins, and that the corresponding state principle applies for some functional modes. Namely, in the hyperthermophilic species, the flexibility of the effec...

}, issn = {15205207}, doi = {10.1021/acs.jpcb.6b00306}, author = {Katava, Marina and Kalimeri, Maria and Guillaume Stirnemann and Fabio Sterpone} } @article {2016|1764, title = {Thermal activation of {\textquoteleft}allosteric-like{\textquoteright} large-scale motions in a eukaryotic Lactate Dehydrogenase.}, journal = {Sci. Reports}, volume = {7}, year = {2016}, pages = {41092}, author = {M. Katava and M. Maccarini and G. Villain and A. Paciaroni and M. Sztucki and O. Ivanova and D. Madern and Fabio Sterpone} } @conference {2016|1608, title = {Toward Microscopic Simulations of Proteins in Cell-Like Environments}, booktitle = {Biophys. J.}, volume = {110}, number = {3, 1}, year = {2016}, note = {60th Annual Meeting of the Biophysical-Society, Los Angeles, CA, FEB 27-MAR 02, 2016}, month = {feb}, pages = {386A}, publisher = {Biophys Soc}, organization = {Biophys Soc}, issn = {0006-3495}, author = {Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {2016|1633, title = {Water Determines the Structure and Dynamics of Proteins}, journal = {Chem. Rev.}, volume = {116}, year = {2016}, pages = {7673{\textendash}7697}, author = {M-C. Bellissent-Funel and A. Hassanali and M. Havenith and R. Henchman and P. Pohl and Fabio Sterpone and D. van der Spoel and Y. Xu and A. E. Garcia} } @article {2015|1737, title = {Algebraic Statistics of Poincar{\'e} Recurrences in a DNA Molecule.}, journal = {Phys. Rev. Lett.}, volume = {115}, year = {2015}, month = {oct}, pages = {188104}, abstract = {

The statistics of Poincar{\'e} recurrences is studied for the base-pair breathing dynamics of an all-atom DNA molecule in a realistic aqueous environment with thousands of degrees of freedom. It is found that at least over five decades in time the decay of recurrences is described by an algebraic law with the Poincar{\'e} exponent close to β=1.2. This value is directly related to the correlation decay exponent ν=β-1, which is close to ν\≈0.15 observed in the time resolved Stokes shift experiments. By applying the virial theorem we analyze the chaotic dynamics in polynomial potentials and demonstrate analytically that an exponent β=1.2 is obtained assuming the dominance of dipole-dipole interactions in the relevant DNA dynamics. Molecular dynamics simulations also reveal the presence of strong low frequency noise with the exponent η=1.6. We trace parallels with the chaotic dynamics of symplectic maps with a few degrees of freedom characterized by the Poincar{\'e} exponent β\∼1.5.

}, issn = {1079-7114}, doi = {10.1103/PhysRevLett.115.188104}, author = {Alexey K Mazur and Shepelyansky, D L} } @article {2015|1634, title = {Amyloid beta Protein and Alzheimer{\textquoteright}s Disease: When Computer Simulations Complement Experimental Studies}, journal = {Chem. Rev.}, volume = {115}, number = {9}, year = {2015}, month = {may}, pages = {3518{\textendash}3563}, doi = {10.1021/cr500638n}, author = {Nasica-Labouze, Jessica and Phuong Hoang Nguyen and Fabio Sterpone and Berthoumieu, Olivia and Buchete, Nicolae-Viorel and Cote, Sebastien and De Simone, Alfonso and Doig, Andrew J. and Faller, Peter and Garcia, Angel and Laio, Alessandro and Li, Mai Suan and Melchionna, Simone and Mousseau, Normand and Mu, Yuguang and Paravastu, Anant and Pasquali, Samuela and Rosenman, David J. and Strodel, Birgit and Tarus, Bogdan and Viles, John H. and Zhang, Tong and Wang, Chunyu and Philippe Derreumaux} } @article {2015|1910, title = {Are coarse-grained models apt to detect protein thermal stability? The case of \{OPEP\} force field}, journal = {J. Non-cryst. Solids}, volume = {407}, year = {2015}, note = {7th IDMRCS: Relaxation in Complex Systems}, pages = {494{\textendash}501}, keywords = {Conformational substates network}, doi = {10.1016/j.jnoncrysol.2014.07.005}, url = {http://www.sciencedirect.com/science/article/pii/S0022309314002889}, author = {Maria Kalimeri and Philippe Derreumaux and Fabio Sterpone} } @article {2015|1635, title = {Combined Experimental and Simulation Studies Suggest a Revised Mode of Action of the Anti-Alzheimer Disease Drug NQ-Trp}, journal = {Chemistry-a European Journal}, volume = {21}, number = {36}, year = {2015}, pages = {12657{\textendash}12666}, doi = {10.1002/chem.201500888}, author = {Berthoumieu, Olivia and Phuong Hoang Nguyen and del Castillo-Frias, Maria P. and Ferre, Sabrina and Tarus, Bogdan and Nasica-Labouze, Jessica and Noel, Sabrina and Saurel, Olivier and Rampon, Claire and Doig, Andrew J. and Philippe Derreumaux and Faller, Peter} } @article {2015|1766, title = {Docking Peptides on Proteins: How to Open a Lock, in the Dark, with a Flexible Key}, journal = {Structure}, volume = {23}, number = {8}, year = {2015}, month = {aug}, pages = {1373{\textendash}1374}, doi = {10.1016/j.str.2015.07.004}, author = {S Sacquin-Mora and Chantal Pr{\'e}vost} } @article {2015|1780, title = {{E}pock: rapid analysis of protein pocket dynamics}, journal = {Bioinformatics}, volume = {31}, number = {9}, year = {2015}, month = {may}, pages = {1478{\textendash}1480}, doi = {10.1093/bioinformatics/btu822}, author = {Laurent, Benoist and Matthieu Chavent and Cragnolini, Tristan and Dahl, Anna Caroline E. and Pasquali, Samuela and Philippe Derreumaux and Sansom, Mark S. P. and Marc Baaden} } @article {2015|1582, title = {The elastic free energy of a tandem modular protein under force.}, journal = {Biochem. Biophys. Res. Comm.}, year = {2015}, pages = {1{\textendash}5}, keywords = {free energy landscape, tandem modular protein}, issn = {0006291X}, doi = {10.1016/j.bbrc.2015.03.051}, url = {http://linkinghub.elsevier.com/retrieve/pii/S0006291X15004866}, author = {Valle-Orero, Jessica and Eckels, Edward and Guillaume Stirnemann and Popa, Ionel and Berkovich, Ronen and Fernandez, Julio M.} } @article {2015|1833, title = {{F}old and flexibility: what can proteins{\textquoteright} mechanical properties tell us about their folding nucleus?}, journal = {J. R. Soc. Interface}, volume = {12}, number = {112}, year = {2015}, month = {nov}, author = {S Sacquin-Mora} } @article {2015|1755, title = {How osmolytes influence hydrophobic polymer conformations: A unified view from experiment and theory.}, journal = {Proc. Natl. Acad. Sci. Usa}, volume = {112}, year = {2015}, pages = {9270{\textendash}5}, abstract = {

It is currently the consensus belief that protective osmolytes such as trimethylamine N-oxide (TMAO) favor protein folding by being excluded from the vicinity of a protein, whereas denaturing osmolytes such as urea lead to protein unfolding by strongly binding to the surface. Despite there being consensus on how TMAO and urea affect proteins as a whole, very little is known as to their effects on the individual mechanisms responsible for protein structure formation, especially hydrophobic association. In the present study, we use single-molecule atomic force microscopy and molecular dynamics simulations to investigate the effects of TMAO and urea on the unfolding of the hydrophobic homopolymer polystyrene. Incorporated with interfacial energy measurements, our results show that TMAO and urea act on polystyrene as a protectant and a denaturant, respectively, while complying with Tanford-Wyman preferential binding theory. We provide a molecular explanation suggesting that TMAO molecules have a greater thermodynamic binding affinity with the collapsed conformation of polystyrene than with the extended conformation, while the reverse is true for urea molecules. Results presented here from both experiment and simulation are in line with earlier predictions on a model Lennard-Jones polymer while also demonstrating the distinction in the mechanism of osmolyte action between protein and hydrophobic polymer. This marks, to our knowledge, the first experimental observation of TMAO-induced hydrophobic collapse in a ternary aqueous system.

}, keywords = {Atomic Force, Computer Simulation, Hydrophobic and Hydrophilic Interactions, Mechanical, Methylamines, Methylamines: chemistry, Microscopy, Molecular Dynamics Simulation, Normal Distribution, Polymers, Polymers: chemistry, Polystyrenes, Polystyrenes: chemistry, Protein Binding, Protein Conformation, Protein Folding, Proteins, Proteins: chemistry, Software, Solvents, Solvents: chemistry, Stress, Thermodynamics, Urea, Urea: chemistry, Water, Water: chemistry}, isbn = {1215421109}, issn = {1091-6490}, doi = {10.1073/pnas.1511780112}, url = {http://www.pnas.org/content/112/30/9270}, author = {Mondal, Jagannath and Halverson, Duncan and Li, Isaac T S and Guillaume Stirnemann and Walker, Gilbert C and Berne, Bruce J} } @article {2015|1965, title = {An integrative approach to the study of filamentous oligomeric assemblies, with application to {R}ec{A}}, journal = {Plos One}, volume = {in press}, year = {2015}, pages = {e0116414}, abstract = {

Oligomeric macromolecules in the cell self-organize into a wide variety of geometrical motifs such as helices, rings or linear filaments. The recombinase proteins involved in homologous recombination present many such assembly motifs. Here, we examine in particular the polymorphic characteristics of RecA, the most studied member of the recombinase family, using an integrative approach that relates local modes of monomer/monomer association to the global architecture of their screw-type organization. In our approach, local modes of association are sampled via docking or Monte Carlo simulations. This enables shedding new light on fiber morphologies that may be adopted by the RecA protein. Two distinct RecA helical morphologies, the so-called \"extended\" and \"compressed\" forms, are known to play a role in homologous recombination. We investigate the variability within each form in terms of helical parameters and steric accessibility. We also address possible helical discontinuities in RecA filaments due to multiple monomer-monomer association modes. By relating local interface organization to global filament morphology, the strategies developed here to study RecA self-assembly are particularly well suited to other DNA-binding proteins and to filamentous protein assemblies in general.

}, doi = {10.1371/journal.pone.0116414}, author = {Benjamin Boyer and Johann Ezelin and Pierre Poulain and A Saladin and Martin Zacharias and Charles H. Robert and Chantal Pr{\'e}vost} } @article {2015|1586, title = {Investigating the Structural Variability and Binding Modes of the Glioma Targeting NFL-TBS.40-63 Peptide on Tubulin}, journal = {Biochemistry}, volume = {54}, number = {23}, year = {2015}, month = {jun}, pages = {3660{\textendash}3669}, doi = {10.1021/acs.biochem5b00146}, author = {Laurin, Y. and Savarin, P. and Charles H. Robert and M. Takahashi and Eyer, J. and Chantal Pr{\'e}vost and S Sacquin-Mora} } @article {2015|1975, title = {{A}llosteric and hyperekplexic mutant phenotypes investigated on an α1 glycine receptor transmembrane structure}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {112}, number = {9}, year = {2015}, month = {mar}, pages = {2865{\textendash}2870}, author = {Moraga-Cid, G. and Sauguet, L. and Huon, C. and Malherbe, L. and Girard-Blanc, C. and Petres, S. and Murail, S. and Antoine Taly and Marc Baaden and Delarue, M. and Corringer, P. J.} } @article {2015|1729, title = {The mechanochemistry of copper reports on the directionality of unfolding in model cupredoxin proteins.}, journal = {Nature Comm.}, volume = {6}, year = {2015}, pages = {7894}, abstract = {

Understanding the directionality and sequence of protein unfolding is crucial to elucidate the underlying folding free energy landscape. An extra layer of complexity is added in metalloproteins, where a metal cofactor participates in the correct, functional fold of the protein. However, the precise mechanisms by which organometallic interactions are dynamically broken and reformed on (un)folding are largely unknown. Here we use single molecule force spectroscopy AFM combined with protein engineering and MD simulations to study the individual unfolding pathways of the blue-copper proteins azurin and plastocyanin. Using the nanomechanical properties of the native copper centre as a structurally embedded molecular reporter, we demonstrate that both proteins unfold via two independent, competing pathways. Our results provide experimental evidence of a novel kinetic partitioning scenario whereby the protein can stochastically unfold through two distinct main transition states placed at the N and C termini that dictate the direction in which unfolding occurs.

}, isbn = {doi:10.1038/ncomms8894}, issn = {2041-1723}, doi = {10.1038/ncomms8894}, url = {http://www.nature.com/ncomms/2015/150803/ncomms8894/abs/ncomms8894.html}, author = {Beedle, Amy E M and Lezamiz, Ainhoa and Guillaume Stirnemann and Garcia-Manyes, Sergi} } @article {2015|1664, title = {Membrane Protein Structure, Function, and Dynamics: a Perspective from Experiments and Theory.}, journal = {J. Membr. Biol.}, volume = {248}, year = {2015}, publisher = {Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou, 11527, Athens, Greece, zcournia@bioacademy.gr.}, chapter = {611}, abstract = {

Membrane proteins mediate processes that are fundamental for the flourishing of biological cells. Membrane-embedded transporters move ions and larger solutes across membranes; receptors mediate communication between the cell and its environment and membrane-embedded enzymes catalyze chemical reactions. Understanding these mechanisms of action requires knowledge of how the proteins couple to their fluid, hydrated lipid membrane environment. We present here current studies in computational and experimental membrane protein biophysics, and show how they address outstanding challenges in understanding the complex environmental effects on the structure, function, and dynamics of membrane proteins.

}, doi = {10.1007/s00232-015-9802-0}, author = {Cournia, Zoe and Allen, Toby W. and Andricioaei, Ioan and Antonny, Bruno and Baum, Daniel and Grace Brannigan and Buchete, Nicolae-Viorel and Deckman, Jason T. and Delemotte, Lucie and Del Val, Coral and Friedman, Ran and Gkeka, Paraskevi and Hege, Hans-Christian and J{\'e}r{\^o}me H{\'e}nin and Kasimova, Marina A. and Kolocouris, Antonios and Michael L Klein and Khalid, Syma and Lemieux, M Joanne and Lindow, Norbert and Roy, Mahua and Selent, Jana and Mounir Tarek and Tofoleanu, Florentina and Vanni, Stefano and Urban, Sinisa and Wales, David J. and Smith, Jeremy C. and Bondar, Ana-Nicoleta} } @article {2015|1549, title = {{N}othing to sneeze at: a dynamic and integrative computational model of an influenza {A} virion}, journal = {Structure}, volume = {23}, number = {3}, year = {2015}, month = {mar}, pages = {584{\textendash}597}, author = {Reddy, T. and Shorthouse, D. and Parton, D. L. and Jefferys, E. and Fowler, P. W. and Matthieu Chavent and Marc Baaden and Sansom, M. S.} } @article {2015|1705, title = {Picosecond dissociation of amyloid fibrils with infrared laser: A nonequilibrium simulation study}, journal = {J. Chem. Phys.}, volume = {143}, number = {15}, year = {2015}, month = {oct}, pages = {155101}, doi = {10.1063/1.4933207}, author = {Man Hoang Viet and Philippe Derreumaux and Mai Suan Li and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2015|1745, title = {Picosecond melting of peptide nanotubes using an infrared laser: a nonequilibrium simulation study}, journal = {Phys. Chem. Chem. Phys.}, volume = {17}, number = {41}, year = {2015}, pages = {27275{\textendash}27280}, doi = {10.1039/c5cp04401d}, author = {Viet, Man Hoang and Phan Minh Truong and Philippe Derreumaux and Li, Mai Suan and Roland, Christopher and Sagui, Celeste and Phuong Hoang Nguyen} } @article {2015|1709, title = {Protein Simulations in Fluids: Coupling the OPEP Coarse-Grained Force Field with Hydrodynamics}, journal = {J. Chem. Theory Comput.}, volume = {11}, number = {4}, year = {2015}, month = {apr}, pages = {1843{\textendash}1853}, doi = {10.1021/ct501015h}, author = {Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {2015|1677, title = {Recovering protein thermal stability using all-atom Hamiltonian replica-exchange simulations in explicit solvent}, journal = {J. Chem. Theo. Comput.}, volume = {11}, year = {2015}, pages = {5573{\textendash}5577}, abstract = {

The REST2 method is successfully applied to investigate the thermal stability of chignolin CLN025 and of Trp-cage. As opposed to temperature replica exchange, REST2 relies on the rescaling of the protein potential energy, which allows a smaller number of replicas. The shape of the stability curve reconstructed on the basis of the corresponding-state principle is in very good agreement with experimental data; for chignolin, the effect of mutations is also recovered.

}, issn = {15499626}, doi = {10.1021/acs.jctc.5b00954}, author = {Guillaume Stirnemann and Fabio Sterpone} } @article {2015|1668, title = {Role of Internal Water on Protein Thermal Stability: The Case of Homologous G Domains.}, journal = {J. Phys. Chem. B}, volume = {119}, year = {2015}, month = {jul}, pages = {8939{\textendash}49}, abstract = {

In this work, we address the question of whether the enhanced stability of thermophilic proteins has a direct connection with internal hydration. Our model systems are two homologous G domains of different stability: the mesophilic G domain of the elongation factor thermal unstable protein from E. coli and the hyperthermophilic G domain of the EF-1α protein from S. solfataricus. Using molecular dynamics simulation at the microsecond time scale, we show that both proteins host water molecules in internal cavities and that these molecules exchange with the external solution in the nanosecond time scale. The hydration free energy of these sites evaluated via extensive calculations is found to be favorable for both systems, with the hyperthermophilic protein offering a slightly more favorable environment to host water molecules. We estimate that, under ambient conditions, the free energy gain due to internal hydration is about 1.3 kcal/mol in favor of the hyperthermophilic variant. However, we also find that, at the high working temperature of the hyperthermophile, the cavities are rather dehydrated, meaning that under extreme conditions other molecular factors secure the stability of the protein. Interestingly, we detect a clear correlation between the hydration of internal cavities and the protein conformational landscape. The emerging picture is that internal hydration is an effective observable to probe the conformational landscape of proteins. In the specific context of our investigation, the analysis confirms that the hyperthermophilic G domain is characterized by multiple states and it has a more flexible structure than its mesophilic homologue.

}, issn = {1520-5207}, doi = {10.1021/jp507571u}, author = {Rahaman, Obaidur and Kalimeri, Maria and Melchionna, Simone and J{\'e}r{\^o}me H{\'e}nin and Fabio Sterpone} } @article {2015|1769, title = {Stay Wet, Stay Stable? How Internal Water Helps the Stability of Thermophilic Proteins}, journal = {The Journal of Physical Chemistry B}, volume = {119}, number = {40}, year = {2015}, pages = {12760{\textendash}12770}, publisher = {American Chemical Society}, author = {Chakraborty, Debashree and Antoine Taly and Fabio Sterpone} } @article {2015|1714, title = {Structures of the Alzheimer{\textquoteright}s Wild-Type A beta 1-40 Dimer from Atomistic Simulations}, journal = {J. Phys. Chem. B}, volume = {119}, number = {33}, year = {2015}, pages = {10478{\textendash}10487}, doi = {10.1021/acs.jpcb.5b05593}, author = {Tarus, Bogdan and Thanh-Thuy Tran and Nasica-Labouze, Jessica and Fabio Sterpone and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2014|1931, title = {Assessing the effect of dynamics on the closed-loop protein-folding hypothesis}, journal = {Journal of the Royal Society Interface}, volume = {11}, number = {91}, year = {2014}, pages = {20130935}, doi = {10.1098/rsif.2013.0935}, url = {http://rsif.royalsocietypublishing.org/content/11/91/20130935.abstract}, author = {Chintapalli, Sree V. and Illingworth, Christopher J. R. and Upton, Graham J. G. and S Sacquin-Mora and Reeves, Philip J. and Mohammedali, Hani S. and Reynolds, Christopher A.} } @proceedings {2014|1577, title = {{BIOIMAGING} 2014 - Proceedings of the International Conference on Bioimaging, ESEO, Angers, Loire Valley, France, 3-6 March, 2014}, year = {2014}, publisher = {SciTePress}, editor = {M{\'a}rio Forjaz Secca and Jan Schier and Guy Plantier and Tanja Schultz and Ana L. N. Fred and Hugo Gamboa} } @article {2014|1751, title = {How force unfolding differs from chemical denaturation.}, journal = {Proc. Natl. Acad. Sci. U.s.a}, volume = {111}, year = {2014}, pages = {3413{\textendash}8}, abstract = {

Single-molecule force spectroscopies are remarkable tools for studying protein folding and unfolding, but force unfolding explores protein configurations that are potentially very different from the ones traditionally explored in chemical or thermal denaturation. Understanding these differences is crucial because such configurations serve as starting points of folding studies, and thus can affect both the folding mechanism and the kinetics. Here we provide a detailed comparison of both chemically induced and force-induced unfolded state ensembles of ubiquitin based on extensive, all-atom simulations of the protein either extended by force or denatured by urea. As expected, the respective unfolded states are very different on a macromolecular scale, being fully extended under force with no contacts and partially extended in urea with many nonnative contacts. The amount of residual secondary structure also differs: A significant population of $\alpha$-helices is found in chemically denatured configurations but such helices are absent under force, except at the lowest applied force of 30 pN where short helices form transiently. We see that typical-size helices are unstable above this force, and $\beta$-sheets cannot form. More surprisingly, we observe striking differences in the backbone dihedral angle distributions for the protein unfolded under force and the one unfolded by denaturant. A simple model based on the dialanine peptide is shown to not only provide an explanation for these striking differences but also illustrates how the force dependence of the protein dihedral angle distributions give rise to the worm-like chain behavior of the chain upon force.

}, keywords = {Chemical, Hydrogen-Ion Concentration, Models, Molecular Dynamics Simulation, Protein Conformation, Protein Denaturation, Protein Folding, Protein Unfolding, Ubiquitin, Ubiquitin: chemistry, Urea, Urea: chemistry}, issn = {1091-6490}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24550471}, author = {Guillaume Stirnemann and Kang, Seung-gu and Zhou, Ruhong and Berne, Bruce J} } @article {2014|1893, title = {Improved PEP-FOLD Approach for Peptide and Miniprotein Structure Prediction}, journal = {J. Chem. Theory Comput.}, volume = {10}, number = {10}, year = {2014}, month = {oct}, pages = {4745{\textendash}4758}, doi = {10.1021/ct500592m}, author = {Shen, Yimin and Maupetit, Julien and Philippe Derreumaux and Pierre Tuffery} } @article {2014|1964, title = {Interface Matters: The Stiffness Route to Stability of a Thermophilic Tetrameric Malate Dehydrogenase}, journal = {Plos One}, volume = {9}, number = {12}, year = {2014}, month = {dec}, pages = {e113895}, url = {http://dx.doi.org/10.1371\%2Fjournal.pone.0113895}, author = {Kalimeri, Maria and Girard, Eric and Madern, Dominique and Sterpone, Fabio} } @article {2014|1937, title = {Motions and mechanics: investigating conformational transitions in multi-domain proteins with coarse-grain simulations}, journal = {Mol. Simul.}, volume = {40}, number = {1-3}, year = {2014}, month = {jan}, pages = {229{\textendash}236}, doi = {10.1080/08927022.2013.843176}, author = {S Sacquin-Mora} } @article {2014|2015, title = {Multiscale Simulations Give Insight into the Hydrogen In and Out Pathways of [NiFe]-Hydrogenases from Aquifex aeolicus and Desulfovibrio fructosovorans}, journal = {J. Phys. Chem. B}, volume = {118}, number = {48}, year = {2014}, month = {dec}, pages = {13800{\textendash}13811}, doi = {10.1021/jp5089965}, author = {Oteri, F and Marc Baaden and Lojou, E and S Sacquin-Mora} } @article {2014|1798, title = {The OPEP protein model: from single molecules, amyloid formation, crowding and hydrodynamics to DNA/RNA systems}, journal = {Chem. Soc. Rev.}, volume = {43}, number = {13}, year = {2014}, pages = {4871{\textendash}4893}, doi = {10.1039/c4cs00048j}, author = {F. Sterpone and S. Melchionna and Pierre Tuffery and S. Pasquali and N. Mousseau and T. Cragnolini and Y Chebaro and J.-F. St-Pierre and M. Kalimeri and A. Barducci and Y. Laurin and A. Tek and Marc Baaden and Phuong Hoang Nguyen and Philippe Derreumaux} } @conference {2014|1760, title = {Optogating a powerful approach to control an ion-channel gate}, booktitle = {PURINERGIC SIGNALLING}, volume = {10}, number = {4}, year = {2014}, pages = {762{\textendash}762}, publisher = {SPRINGER VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS}, organization = {SPRINGER VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS}, author = {Lemoine, Damien and Habermacher, Chlo{\'e} and Martz, Adeline and M{\'e}ry, Pierre-Fran\c cois and Bouquier, Nathalie and Diverchy, Fanny and Antoine Taly and Rassendren, Fran\c cois and Specht, Alexandre and Grutter, Thomas} } @article {2014|1598, title = {A predicted binding site for cholesterol on the GABAA receptor.}, journal = {Biophys. J.}, volume = {106}, number = {9}, year = {2014}, month = {may}, pages = {1938{\textendash}1949}, publisher = {Department of Physics, Rutgers University-Camden, Camden, New Jersey; Center for Computational and Integrative Biology, Rutgers University-Camden, Camden, New Jersey. Electronic address: Grace.Brannigan@rutgers.edu.}, abstract = {Modulation of the GABA type A receptor (GABAAR) function by cholesterol and other steroids is documented at the functional level, yet its structural basis is largely unknown. Current data on structurally related modulators suggest that cholesterol binds to subunit interfaces between transmembrane domains of the GABAAR. We construct homology models of a human GABAAR based on the structure of the glutamate-gated chloride channel GluCl of Caenorhabditis elegans. The models show the possibility of previously unreported disulfide bridges linking the M1 and M3 transmembrane helices in the α and γ subunits. We discuss the biological relevance of such disulfide bridges. Using our models, we investigate cholesterol binding to intersubunit cavities of the GABAAR transmembrane domain. We find that very similar binding modes are predicted independently by three approaches: analogy with ivermectin in the GluCl crystal structure, automated docking by AutoDock, and spontaneous rebinding events in unbiased molecular dynamics simulations. Taken together, the models and atomistic simulations suggest a somewhat flexible binding mode, with several possible orientations. Finally, we explore the possibility that cholesterol promotes pore opening through a wedge mechanism.}, keywords = {Amino Acid, Binding Sites, Caenorhabditis elegans Proteins, chemistry, chemistry/metabolism, Chloride Channels, Cholesterol, GABA-A, Humans, Hydrogen Bonding, Ivermectin, metabolism, Molecular Docking Simulation, Molecular Dynamics Simulation, Porosity, Protein Binding, Protein Conformation, Receptors, Sequence Homology, Substrate Specificity}, doi = {10.1016/j.bpj.2014.03.024}, author = {J{\'e}r{\^o}me H{\'e}nin and Salari, Reza and Murlidaran, Sruthi and Grace Brannigan} } @article {2014|1518, title = {{T}he weak, fluctuating, dipole moment of membrane-bound hydrogenase from {A}quifex aeolicus accounts for its adaptability to charged electrodes}, journal = {Phys. Chem. Chem. Phys.}, volume = {16}, number = {23}, year = {2014}, month = {may}, pages = {11318{\textendash}11322}, author = {Oteri, F and Ciaccafava, A and Poulpiquet, A and Marc Baaden and Lojou, E and S Sacquin-Mora} } @article {2014|1905, title = {Theoretical study of the NLO responses of some natural and unnatural amino acids used as probe molecules}, journal = {J. Mol. Model.}, volume = {20}, number = {8}, year = {2014}, month = {aug}, pages = {2388}, doi = {10.1007/s00894-014-2388-0}, author = {Derrar, S. N. and Sekkal-Rahal, M. and Philippe Derreumaux and Springborg, M.} } @conference {2014|1783, title = {Wide Exploration of OPEP Protein Energy Landscapes using Advanced Monte Carlo Methods}, booktitle = {Biophys. J.}, volume = {106}, number = {2, 1}, year = {2014}, note = {58th Annual Meeting of the Biophysical-Society, San Francisco, CA, FEB 15-19, 2014}, month = {jan}, pages = {256A}, author = {Cragnolini, Tristan and Sutherland-Cash, Kyle H. and Wales, David and Pasquali, Samuela and Philippe Derreumaux} } @article {2013|1938, title = {Allosteric signaling and dynamics of the clamshell-like NMDA receptor GluN1 N-terminal domain}, journal = {Nature Structural \& Molecular Biology}, volume = {20}, number = {4}, year = {2013}, pages = {477{\textendash}485}, publisher = {Nature Publishing Group}, author = {Zhu, Shujia and Stroebel, David and Yao, C Andrea and Antoine Taly and Paoletti, Pierre} } @article {2013|1797, title = {Biomolecular hydration dynamics: a jump model perspective}, journal = {Chem. Soc. Rev.}, volume = {42}, number = {13}, year = {2013}, pages = {5672{\textendash}5683}, author = {Fogarty, Aoife C. and Elise Dubou{\'e}-Dijon and Sterpone, Fabio and Hynes, James T. and Laage, Damien} } @article {2013|1904, title = {Density functional conformational study of 2-O-sulfated 3,6 anhydro-alpha-D-galactose and of neo-kappa- and iota-carrabiose molecules in gas phase and water}, journal = {J. Mol. Model.}, volume = {19}, number = {2}, year = {2013}, month = {feb}, pages = {893{\textendash}904}, doi = {10.1007/s00894-012-1621-y}, author = {Bestaoui-Berrekhchi-Berrahma, Noreya and Philippe Derreumaux and Sekkal-Rahal, Majda and Springborg, Michael and Sayede, Adlane and Yousfi, Noureddine and Kadoun, Abd-Ed-Daim} } @article {2013|1956, title = {The effect of protein composition on hydration dynamics}, journal = {Phys. Chem. Chem. Phys.}, volume = {15}, number = {10}, year = {2013}, pages = {3570{\textendash}3576}, publisher = {The Royal Society of Chemistry}, abstract = {Water dynamics at the surface of two homologous proteins with different thermal resistances is found to be unaffected by the different underlying amino-acid compositions{,} and when proteins are folded it responds similarly to temperature variations. Upon unfolding the water dynamics slowdown with respect to bulk decreases by a factor of two. Our findings are explained by the dominant topological perturbation induced by the protein on the water hydrogen bond dynamics.}, author = {Rahaman, O. and Melchionna, S. and Laage, D. and Sterpone, F.} } @article {2013|1752, title = {Elasticity, structure, and relaxation of extended proteins under force.}, journal = {Proc. Natl. Acad. Sci. U.s.a}, volume = {110}, year = {2013}, pages = {3847{\textendash}52}, abstract = {

Force spectroscopies have emerged as a powerful and unprecedented tool to study and manipulate biomolecules directly at a molecular level. Usually, protein and DNA behavior under force is described within the framework of the worm-like chain (WLC) model for polymer elasticity. Although it has been surprisingly successful for the interpretation of experimental data, especially at high forces, the WLC model lacks structural and dynamical molecular details associated with protein relaxation under force that are key to the understanding of how force affects protein flexibility and reactivity. We use molecular dynamics simulations of ubiquitin to provide a deeper understanding of protein relaxation under force. We find that the WLC model successfully describes the simulations of ubiquitin, especially at higher forces, and we show how protein flexibility and persistence length, probed in the force regime of the experiments, are related to how specific classes of backbone dihedral angles respond to applied force. Although the WLC model is an average, backbone model, we show how the protein side chains affect the persistence length. Finally, we find that the diffusion coefficient of the protein{\textquoteright}s end-to-end distance is on the order of 10(8) nm(2)/s, is position and side-chain dependent, but is independent of the length and independent of the applied force, in contrast with other descriptions.

}, keywords = {Atomic Force, Biophysical Phenomena, Computer Simulation, Elasticity, Mechanical, Microscopy, Models, Molecular, Molecular Dynamics Simulation, Proteins, Proteins: chemistry, Stress, Ubiquitin, Ubiquitin: chemistry}, issn = {1091-6490}, url = {http://www.pnas.org/content/early/2013/02/13/1300596110.abstract}, author = {Guillaume Stirnemann and Giganti, David and Fernandez, Julio M and Berne, B J} } @article {2013|1525, title = {{F}ormation of raft-like assemblies within clusters of influenza hemagglutinin observed by {M}{D} simulations}, journal = {Plos Comput. Biol.}, volume = {9}, number = {4}, year = {2013}, month = {apr}, pages = {e1003034}, author = {Parton, D. L. and Tek, A. and Marc Baaden and Sansom, M. S.} } @article {2013|1974, title = {{A} gating mechanism of pentameric ligand-gated ion channels}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {110}, number = {42}, year = {2013}, month = {oct}, pages = {E3987{\textendash}3996}, author = {Calimet, N. and Simoes, M. and Changeux, J. P. and Karplus, M. and Antoine Taly and Cecchini, M.} } @article {2013|1700, title = {Heme orientation modulates histidine dissociation and ligand binding kinetics in the hexacoordinated human neuroglobin}, journal = {J. Biol. Inorg. Chem.}, volume = {18}, number = {1}, year = {2013}, pages = {111{\textendash}122}, doi = {10.1007/s00775-012-0956-2}, author = {Bocahut, A. and Derrien, V. and Bernad, S. and Sebban, P. and S Sacquin-Mora and Guittet, E. and Lescop, E.} } @article {2013|1926, title = {How Conformational Flexibility Stabilizes the Hyperthermophilic Elongation Factor G-Domain}, journal = {J. Phys. Chem. B}, volume = {117}, number = {44}, year = {2013}, month = {nov}, pages = {13775{\textendash}13785}, author = {Kalimeri, Maria and Rahaman, Obaidur and Melchionna, Simone and Sterpone, Fabio} } @article {2013|1892, title = {Importance of the Ion-Pair Interactions in the OPEP Coarse-Grained Force Field: Parametrization and Validation}, journal = {J. Chem. Theory Comput.}, volume = {9}, number = {10}, year = {2013}, month = {oct}, pages = {4574{\textendash}4584}, doi = {10.1021/ct4003493}, author = {Sterpone, Fabio and Phuong Hoang Nguyen and Kalimeri, Maria and Philippe Derreumaux} } @inbook {2013|1533, title = {Inquiring Protein Thermostability: Is Resistance to Temperature Stress a Rigidity/Flexibility Trade-off?}, booktitle = {Proceedings of the European Conference on Complex Systems 2012}, year = {2013}, publisher = {Springer International Publishing}, organization = {Springer International Publishing}, author = {Kalimeri, Maria and Melchionna, Simone and Sterpone, Fabio} } @article {2013|1670, title = {Mechanisms of acceleration and retardation of water dynamics by ions}, journal = {J. Am. Chem. Soc.}, volume = {135}, year = {2013}, pages = {11824{\textendash}11831}, abstract = {

There are fundamental and not yet fully resolved questions concerning the impact of solutes, ions in particular, on the structure and dynamics of water, which can be formulated as follows: Are the effects of ions local or long-ranged? Is the action of cations and anions on water cooperative or not? Here, we investigate how the reorientation and hydrogen-bond dynamics of water are affected by ions in dilute and concentrated aqueous salt solutions. By combining simulations and analytic modeling, we first show that ions have a short-ranged influence on the reorientation of individual water molecules and that depending on their interaction strength with water, they may accelerate or slow down water dynamics. A simple additive picture combining the effects of the cations and anions is found to provide a good description in dilute solutions. In concentrated solutions, we show that the average water reorientation time ceases to scale linearly with salt concentration due to overlapping hydration shells and structural rearrangements which reduce the translational displacements induced by hydrogen-bond switches and increase the solution viscosity. This effect is not ion-specific and explains why all concentrated salt solutions slow down water dynamics. Our picture, which is demonstrated to be robust vis-a-vis a change in the force-field, reconciles the seemingly contradictory experimental results obtained by ultrafast infrared and NMR spectroscopies, and suggests that there are no long-ranged cooperative ion effects on the dynamics of individual water molecules in dilute solutions.

}, issn = {00027863}, author = {Guillaume Stirnemann and Wernersson, Erik and Jungwirth, Pavel and Laage, Damien} } @article {2013|1747, title = {A mutation causes MuSK reduced sensitivity to agrin and congenital myasthenia}, journal = {Plos One}, volume = {8}, number = {1}, year = {2013}, publisher = {Public Library of Science}, author = {Ammar, A Ben and Soltanzadeh, Payam and Bauch{\'e}, St{\'e}phanie and Richard, Pascale and Goillot, Evelyne and Herbst, Ruth and Gaudon, Karen and Huz{\'e}, Caroline and Schaeffer, Laurent and Yamanashi, Yuji and others} } @article {2013|1973, title = {{O}ptical control of an ion channel gate}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {110}, number = {51}, year = {2013}, month = {dec}, pages = {20813{\textendash}20818}, author = {Lemoine, D. and Habermacher, C. and Martz, A. and Mery, P. F. and Bouquier, N. and Diverchy, F. and Antoine Taly and Rassendren, F. and Specht, A. and Grutter, T.} } @article {2013|1961, title = {Protein-protein interactions in a crowded environment: an analysis via cross-docking simulations and evolutionary information}, journal = {Plos Comput. Biol.}, volume = {9}, number = {12}, year = {2013}, month = {dec}, pages = {e1003369}, doi = {10.1371/journal.pcbi.1003369}, url = {http://hal.inria.fr/hal-00875116}, author = {Lopes, Anne and S Sacquin-Mora and Dimitrova, Viktoriya and Laine, Elodie and Ponty, Yann and Carbone, Alessandra} } @article {2013|1406, title = {{S}tructural basis for ion permeation mechanism in pentameric ligand-gated ion channels}, journal = {Embo J.}, volume = {32}, number = {5}, year = {2013}, month = {mar}, pages = {728{\textendash}741}, author = {Sauguet, L. and Poitevin, F. and Murail, S. and Van Renterghem, C. and Moraga-Cid, G. and Malherbe, L. and Thompson, A. W. and Koehl, P. and Corringer, P. J. and Marc Baaden and Delarue, M.} } @article {2013|1689, title = {When Does Trimethylamine N-Oxide Fold a Polymer Chain and Urea Unfold It?}, journal = {J. Phys. Chem. B}, volume = {117}, year = {2013}, pages = {8723{\textendash}8732}, abstract = {

Longstanding mechanistic questions about the role of protecting osmolyte trimethylamine N-oxide (TMAO) that favors protein folding and the denaturing osmolyte urea are addressed by studying their effects on the folding of uncharged polymer chains. Using atomistic molecular dynamics simulations, we show that 1 M TMAO and 7 M urea solutions act dramatically differently on these model polymer chains. Their behaviors are sensitive to the strength of the attractive dispersion interactions of the chain with its environment: when these dispersion interactions are sufficiently strong, TMAO suppresses the formation of extended conformations of the hydrophobic polymer as compared to water while urea promotes the formation of extended conformations. Similar trends are observed experimentally for real protein systems. Quite surprisingly, we find that both protecting and denaturing osmolytes strongly interact with the polymer, seemingly in contrast with existing explanations of the osmolyte effect on proteins. We show that what really matters for a protective osmolyte is its effective depletion as the polymer conformation changes, which leads to a negative change in the preferential binding coefficient. For TMAO, there is a much more favorable free energy of insertion of a single osmolyte near collapsed conformations of the polymer than near extended conformations. By contrast, urea is preferentially stabilized next to the extended conformation and thus has a denaturing effect.

}, isbn = {15206106}, url = {http://pubs.acs.org/doi/abs/10.1021/jp405609j$\backslash$nhttp://pubs.acs.org/doi/pdf/10.1021/jp405609j$\backslash$nhttp://dx.doi.org/10.1021/jp405609j}, author = {Mondal, Jagannath and Guillaume Stirnemann and Berne, B J} } @article {2012|1934, title = {{ATTRACT} and {PTOOLS}: {O}pen source programs for protein-protein docking}, journal = {Methods Mol. Biol.}, volume = {819}, year = {2012}, pages = {221{\textendash}232}, abstract = {

The prediction of the structure of protein-protein complexes based on structures or structural models of isolated partners is of increasing importance for structural biology and bioinformatics. The ATTRACT program can be used to perform systematic docking searches based on docking energy minimization. It is part of the object-oriented PTools library written in Python and C++. The library contains various routines to manipulate protein structures, to prepare and perform docking searches as well as analyzing docking results. It also intended to facilitate further methodological developments in the area of macromolecular docking that can be easily integrated. Here, we describe the application of PTools to perform systematic docking searches and to analyze the results. In addition, the possibility to perform multi-component docking will also be presented.

}, doi = {10.1007/978-1-61779-465-0_15}, author = {Schneider, S. and A Saladin and Fiorucci, S. and Chantal Pr{\'e}vost and Martin Zacharias} } @article {2012|1676, title = {Communication: On the origin of the non-Arrhenius behavior in water reorientation dynamics}, journal = {J. Chem. Phys.}, volume = {137}, year = {2012}, abstract = {

We combine molecular dynamics simulations and analytic modeling to determine the origin of the non-Arrhenius temperature dependence of liquid water{\textquoteright}s reorientation and hydrogen-bond dynamics between 235 K and 350 K. We present a quantitative model connecting hydrogen-bond exchange dynamics to local structural fluctuations, measured by the asphericity of Voronoi cells associated with each water molecule. For a fixed local structure the regular Arrhenius behavior is recovered, and the global anomalous temperature dependence is demonstrated to essentially result from a continuous shift in the unimodal structure distribution upon cooling. The non-Arrhenius behavior can thus be explained without invoking an equilibrium between distinct structures. In addition, the large width of the homogeneous structural distribution is shown to cause a growing dynamical heterogeneity and a non-exponential relaxation at low temperature.

}, issn = {00219606}, author = {Guillaume Stirnemann and Laage, Damien} } @article {2012|1911, title = {Delivering the native structures of peptides from computer simulations and predicted NMR proton chemical shifts}, journal = {J. Pept. Sci.}, volume = {18}, number = {1}, year = {2012}, month = {sep}, pages = {S38}, author = {Thevenet, P. and Shen, Y. and Maupetit, J. and Guyon, F. and Padilla, A. and Philippe Derreumaux and Pierre Tuffery} } @article {2012|1554, title = {Early Stage of the Dehydrogenation of NaAlH4 by Ab Initio Rare Event Simulations}, journal = {The Journal of Physical Chemistry C}, volume = {116}, number = {37}, year = {2012}, pages = {19636{\textendash}19643}, doi = {10.1021/jp3019588}, author = {Sterpone, Fabio and Bonella, Sara and Meloni, Simone} } @article {2012|1793, title = {{I}ntermediate closed channel state(s) precede(s) activation in the {A}{T}{P}-gated {P}2{X}2 receptor}, journal = {Channels (austin)}, volume = {6}, number = {5}, year = {2012}, pages = {398{\textendash}402}, author = {Jiang, R. and Antoine Taly and Lemoine, D. and Martz, A. and Specht, A. and Grutter, T.} } @article {2012|2004, title = {Ligand-gated ion channels: new insights into neurological disorders and ligand recognition}, journal = {Chem. Rev.}, volume = {112}, number = {12}, year = {2012}, month = {sep}, pages = {6285{\textendash}6318}, publisher = {American Chemical Society}, author = {Lemoine, Damien and Jiang, Ruotian and Antoine Taly and Chataigneau, Thierry and Specht, Alexandre and Grutter, Thomas} } @article {2012|1488, title = {Magnitude and molecular origin of water slowdown next to a protein}, journal = {J. Am. Chem. Soc.}, volume = {134}, year = {2012}, pages = {4116{\textendash}4119}, abstract = {

Hydration shell dynamics plays a critical role in protein folding and biochemical activity and has thus been actively studied through a broad range of techniques. While all observations concur with a slowdown of water dynamics relative to the bulk, the magnitude and molecular origin of this retardation remain unclear. Via numerical simulations and theoretical modeling, we establish a molecular description of protein hydration dynamics and identify the key protein features that govern it. Through detailed microscopic mapping of the water reorientation and hydrogen-bond (HB) dynamics around lysozyme, we first determine that 80\% of the hydration layer waters experience a moderate slowdown factor of \~{}2-3, while the slower residual population is distributed along a power-law tail, in quantitative agreement with recent NMR results. We then establish that the water reorientation mechanism at the protein interface is dominated by large angular jumps similar to the bulk situation. A theoretical extended jump model is shown to provide the first rigorous determination of the two key contributions to the observed slowdown: a topological excluded-volume factor resulting from the local protein geometry, which governs the dynamics of the fastest 80\% of the waters, and a free energetic factor arising from the water-protein HB strength, which is especially important for the remaining waters in confined sites at the protein interface. These simple local factors are shown to provide a nearly quantitative description of the hydration shell dynamics.

}, issn = {00027863}, author = {Fabio Sterpone and Guillaume Stirnemann and Laage, Damien} } @article {2012|1506, title = {A novel Locally Closed Conformation of a Bacterial Pentameric Proton-gated Ion Channel}, journal = {Nature Structural \& Molecular Biology}, year = {2012}, month = {apr}, author = {M. Prevost and L. Sauguet and H. Nury and C. Van Renterghem and C. Huon and F. Poitevin and Marc Baaden and M. Delarue and P.-J. Corringer} } @article {2012|1944, title = {PEP-FOLD: an updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides}, journal = {Nucleic Acids Res.}, volume = {40}, number = {W1}, year = {2012}, month = {jul}, pages = {W288-W293}, doi = {10.1093/nar/gks419}, author = {Thevenet, Pierre and Shen, Yimin and Maupetit, Julien and Guyon, Frederic and Philippe Derreumaux and Pierre Tuffery} } @article {2012|1753, title = {Rate limit of protein elastic response is tether dependent}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {109}, year = {2012}, pages = {14416{\textendash}14421}, abstract = {

The elastic restoring force of tissues must be able to operate over the very wide range of loading rates experienced by living organisms. It is surprising that even the fastest events involving animal muscle tissues do not surpass a few hundred hertz. We propose that this limit is set in part by the elastic dynamics of tethered proteins extending and relaxing under a changing load. Here we study the elastic dynamics of tethered proteins using a fast force spectrometer with sub-millisecond time resolution, combined with Brownian and Molecular Dynamics simulations. We show that the act of tethering a polypeptide to an object, an inseparable part of protein elasticity in vivo and in experimental setups, greatly reduces the attempt frequency with which the protein samples its free energy. Indeed, our data shows that a tethered polypeptide can traverse its free-energy landscape with a surprisingly low effective diffusion coefficient D(eff) \~{} 1,200 nm(2)/s. By contrast, our Molecular Dynamics simulations show that diffusion of an isolated protein under force occurs at D(eff) \~{} 10(8) nm(2)/s. This discrepancy is attributed to the drag force caused by the tethering object. From the physiological time scales of tissue elasticity, we calculate that tethered elastic proteins equilibrate in vivo with D(eff) \~{} 10(4)-10(6) nm(2)/s which is two to four orders magnitude smaller than the values measured for untethered proteins in bulk.

}, issn = {0027-8424}, author = {Berkovich, R. and Hermans, R. I. and Popa, I. and Guillaume Stirnemann and Garcia-Manyes, S. and Berne, B. J. and Fernandez, J. M.} } @article {2012|1995, title = {Structural and Spectroscopic Properties of Water around Small Hydrophobic Solutes}, journal = {The Journal of Physical Chemistry B}, volume = {116}, number = {38}, year = {2012}, pages = {11695{\textendash}11700}, doi = {10.1021/jp303213m}, author = {Montagna, Maria and Sterpone, Fabio and Guidoni, Leonardo} } @article {2012|2016, title = {{T}hermal fluctuations of haemoglobin from different species: adaptation to temperature via conformational dynamics}, journal = {J. R. Soc. Interface}, volume = {9}, number = {76}, year = {2012}, month = {nov}, pages = {2845{\textendash}2855}, doi = {10.1098/rsif.2012.0364}, author = {Stadler, A. M. and Garvey, C. J. and Bocahut, A. and S Sacquin-Mora and Digel, I. and Schneider, G. J. and Natali, F. and Artmann, G. M. and Zaccai, G.} } @article {2012|1816, title = {Theoretical study on a series of push-pull molecules grafted on methacrylate copolymers serving for nonlinear optics}, journal = {Int. J. Quantum Chem.}, volume = {112}, number = {15}, year = {2012}, month = {aug}, pages = {2735{\textendash}2742}, doi = {10.1002/qua.23299}, author = {Derrar, S. N. and Sekkal-Rahal, M. and Guemra, K. and Philippe Derreumaux} } @article {2012|1795, title = {Thermophilic proteins: insight and perspective from in silico experiments}, journal = {Chem. Soc. Rev.}, volume = {41}, year = {2012}, pages = {1665{\textendash}1676}, publisher = {The Royal Society of Chemistry}, abstract = {Proteins from thermophilic and hyperthermophilic organisms are stable and function at high temperatures (50-100 [degree]C). The importance of understanding the microscopic mechanisms underlying this thermal resistance is twofold: it is key for acquiring general clues on how proteins maintain their fold stable and for targeting those medical and industrial applications that aim at designing enzymes that can work under harsh conditions. In this tutorial review we first provide the general background of protein thermostability by specifically focusing on the structural and thermodynamic peculiarities; next{,} we discuss how computational studies based on Molecular Dynamics simulations can broaden and refine our knowledge on such special class of proteins.}, author = {Sterpone, Fabio and Melchionna, Simone} } @article {2012|1684, title = {Water jump reorientation and ultrafast vibrational spectroscopy}, journal = {J. Photochem. Photobiol. A}, volume = {234}, year = {2012}, pages = {75{\textendash}82}, abstract = {

The reorganization of water{\textquoteright}s hydrogen-bond (HB) network by breaking and making HBs lies at the heart of many of the pure liquid{\textquoteright}s special features and many aqueous media phenomena, including chemical reactions, ion transport and protein activity. An essential role in this reorganization is played by water molecule reorientation, long described by very small angular displacement Debye rotational diffusion. A markedly contrasting picture has been recently proposed, based on simulation and analytic modeling: a sudden, large amplitude jump mechanism, in which the reorienting water molecule rapidly exchanges HB partners in an activated process which has all the hallmarks of a chemical reaction. In this contribution, we offer a brief review of the jump mechanism together with a discussion of its application to, and probing by, modern ultrafast infrared spectroscopy experiments. Special emphasis is given to the direct characterization of the jumps via pioneering two-dimensional infrared spectroscopic measurements. ?? 2012 Elsevier B.V. All rights reserved.

}, keywords = {Hydrogen-bond dynamics, Pump-probe infrared spectroscopy, Two-dimensional infrared spectroscopy, Water dynamics}, issn = {10106030}, author = {Laage, Damien and Guillaume Stirnemann and Hynes, James T.} } @article {2012, title = {Water Jump Reorientation: From Theoretical Prediction to Experimental Observation}, journal = {Acc. Chem. Res.}, volume = {45}, number = {1}, year = {2012}, pages = {53{\textendash}62}, doi = {10.1021/ar200075u}, author = {Laage, Damien and Guillaume Stirnemann and Sterpone, Fabio and Hynes, James T.} } @article {2011|1654, title = {Accounting for large amplitude protein deformation during in silico macromolecular docking}, journal = {Int. J. Mol. Sci.}, volume = {12}, year = {2011}, pages = {1316{\textendash}33}, abstract = {

Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA. We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

}, keywords = {flexibility, macromolecular docking, protein loops and domains}, doi = {10.3390/ijms12021316}, author = {Bastard, Karine and A Saladin and Chantal Pr{\'e}vost} } @article {2011|1653, title = {On the characterization and selection of diverse conformational ensembles with applications to flexible docking}, journal = {Ieee/acm Trans. Comput. Biol. Bioinform.}, volume = {8}, year = {2011}, pages = {487{\textendash}98}, abstract = {

To address challenging flexible docking problems, a number of docking algorithms pregenerate large collections of candidate conformers. To remove the redundancy from such ensembles, a central problem in this context is to report a selection of conformers maximizing some geometric diversity criterion. We make three contributions to this problem. First, we resort to geometric optimization so as to report selections maximizing the molecular volume or molecular surface area (MSA) of the selection. Greedy strategies are developed, together with approximation bounds. Second, to assess the efficacy of our algorithms, we investigate two conformer ensembles corresponding to a flexible loop of four protein complexes. By focusing on the MSA of the selection, we show that our strategy matches the MSA of standard selection methods, but resorting to a number of conformers between one and two orders of magnitude smaller. This observation is qualitatively explained using the Betti numbers of the union of balls of the selection. Finally, we replace the conformer selection problem in the context of multiple-copy flexible docking. On the aforementioned systems, we show that using the loops selected by our strategy can improve the result of the docking process.

}, doi = {10.1109/TCBB.2009.59}, author = {Loriot, S{\'e}bastien and Sachdeva, Sushant and Bastard, Karine and Chantal Pr{\'e}vost and Fr{\'e}d{\'e}ric Cazals} } @mastersthesis {2011|1574, title = {Coarse-grain models for proteins: Mechanical properties and interactions}, year = {2011}, note = {HDR d{\'e}livr{\'e}e par l{\textquoteright}UFR Sciences du Vivant}, month = {dec}, school = {Universit{\'e} Paris-Diderot - Paris VII}, type = {phdHabilitation {\`a} diriger des recherches}, keywords = {Computational biology, docking, elastic networks, interactions prot{\'e}iques, m{\'e}canique des prot{\'e}ines, Mod{\'e}lisation mol{\'e}culaire, protein interactions, protein mechanics, r{\'e}seau {\'e}lastique}, url = {https://tel.archives-ouvertes.fr/tel-00652917}, author = {S Sacquin-Mora} } @article {2011|1771, title = {Coherent Excitation Transfer Driven by Torsional Dynamics: a Model Hamiltonian for PPV Type Systems}, journal = {Zeitschrift F{\"u}r Physikalische Chemie}, volume = {255}, year = {2011}, pages = {541{\textendash}551}, author = {Fabio Sterpone and R. Martinazzo and A.N. Panda and I. Burghardt} } @article {2011|1473, title = {Coherent vibrational energy transfer along a peptide helix}, journal = {J. Chem. Phys.}, volume = {134}, number = {12}, year = {2011}, month = {mar}, author = {Kobus, Maja and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2011|1665, title = {Community-wide assessment of protein-interface modeling suggests improvements to design methodology.}, journal = {J. Mol. Biol.}, volume = {414}, year = {2011}, month = {nov}, pages = {289{\textendash}302}, abstract = {

The CAPRI (Critical Assessment of Predicted Interactions) and CASP (Critical Assessment of protein Structure Prediction) experiments have demonstrated the power of community-wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community-wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting that there may be important physical chemistry missing in the energy calculations. A total of 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the nonpolar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were, on average, structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a nonbinder.

}, keywords = {Binding Sites, Models, Molecular, Protein Binding, Proteins}, issn = {1089-8638}, doi = {10.1016/j.jmb.2011.09.031}, author = {Fleishman, Sarel J and Whitehead, Timothy A and Strauch, Eva-Maria and Corn, Jacob E and Qin, Sanbo and Zhou, Huan-Xiang and Mitchell, Julie C and Demerdash, Omar N A and Takeda-Shitaka, Mayuko and Terashi, Genki and Moal, Iain H and Li, Xiaofan and Bates, Paul A and Martin Zacharias and Park, Hahnbeom and Ko, Jun-su and Lee, Hasup and Seok, Chaok and Bourquard, Thomas and Bernauer, Julie and Poupon, Anne and Az{\'e}, J{\'e}r{\^o}me and Soner, Seren and Ovali, Sefik Kerem and Ozbek, Pemra and Tal, Nir Ben and Haliloglu, T{\"u}rkan and Hwang, Howook and Vreven, Thom and Pierce, Brian G and Weng, Zhiping and P{\'e}rez-Cano, Laura and Pons, Carles and Fern{\'a}ndez-Recio, Juan and Jiang, Fan and Yang, Feng and Gong, Xinqi and Cao, Libin and Xu, Xianjin and Liu, Bin and Wang, Panwen and Li, Chunhua and Wang, Cunxin and Charles H. Robert and Guharoy, Mainak and Liu, Shiyong and Huang, Yangyu and Li, Lin and Guo, Dachuan and Chen, Ying and Xiao, Yi and London, Nir and Itzhaki, Zohar and Schueler-Furman, Ora and Inbar, Yuval and Potapov, Vladimir and Cohen, Mati and Schreiber, Gideon and Tsuchiya, Yuko and Kanamori, Eiji and Standley, Daron M and Nakamura, Haruki and Kinoshita, Kengo and Driggers, Camden M and Hall, Robert G and Morgan, Jessica L and Hsu, Victor L and Zhan, Jian and Yang, Yuedong and Zhou, Yaoqi and Kastritis, Panagiotis L and Bonvin, Alexandre M J J and Zhang, Weiyi and Camacho, Carlos J and Kilambi, Krishna P and Sircar, Aroop and Gray, Jeffrey J and Ohue, Masahito and Uchikoga, Nobuyuki and Matsuzaki, Yuri and Ishida, Takashi and Akiyama, Yutaka and Khashan, Raed and Bush, Stephen and Fouches, Denis and Tropsha, Alexander and Esquivel-Rodr{\'\i}guez, Juan and Kihara, Daisuke and Stranges, P Benjamin and Jacak, Ron and Kuhlman, Brian and Huang, Sheng-You and Zou, Xiaoqin and Wodak, Shoshana J and Janin, Jo{\"e}l and Baker, David} } @article {2011|1690, title = {Dynamics of water in concentrated solutions of amphiphiles: Key roles of local structure and aggregation}, journal = {J. Phys. Chem. B}, volume = {115}, year = {2011}, pages = {3254{\textendash}3262}, abstract = {

Water translational and reorientational dynamics in concentrated solutions of amphiphiles are investigated through molecular dynamics simulations and analytic modeling. We evidence the critical importance of the solute concentration in determining the magnitude of the slowdown in water dynamics compared to the bulk situation. The comparison of concentrated aqueous solutions of tetramethylurea, which tends to aggregate, and of trimethylamine N-oxide, which does not, shows the dramatic impact of solute clustering on the water dynamics. No significant decoupling of the reorientation and translation dynamics of water is observed, even at very high solute concentrations. The respective roles of energetic and topological disorders in determining the translational subdiffusive water dynamics in these confining environments are discussed. The water reorientational dynamics is shown to be quantitatively described by an extended jump model which combines two factors determined by the local structure: the transition-state excluded volume and the transition-state hydrogen-bond strength.

}, issn = {15206106}, author = {Guillaume Stirnemann and Fabio Sterpone and Laage, Damien} } @article {2011|1612, title = {Enzyme Closure and Nucleotide Binding Structurally Lock Guanylate Kinase}, journal = {Biophys. J.}, volume = {101}, number = {6}, year = {2011}, pages = {1440{\textendash}1449}, doi = {10.1016/j.bpj.2011.07.048}, author = {Delalande, O. and S Sacquin-Mora and Marc Baaden} } @inbook {2011|1573, title = {Exploring the energy landscape of small peptides and proteins by molecular dynamics simulations}, year = {2011}, publisher = {Wiley}, organization = {Wiley}, author = {G. Stock and A. Jain and L. Riccardi and Phuong Hoang Nguyen}, editor = {R. Schweitzer-Stenner} } @article {2011|1446, title = {{F}rontier residues lining globin internal cavities present specific mechanical properties}, journal = {J. Am. Chem. Soc.}, volume = {133}, year = {2011}, month = {jun}, pages = {8753{\textendash}8761}, author = {Bocahut, A. and Bernad, S. and Sebban, P. and S Sacquin-Mora} } @article {2011|1972, title = {{A}gonist trapped in {A}{T}{P}-binding sites of the {P}2{X}2 receptor}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {108}, number = {22}, year = {2011}, month = {may}, pages = {9066{\textendash}9071}, author = {Jiang, R. and Lemoine, D. and Martz, A. and Antoine Taly and Gonin, S. and Prado de Carvalho, L. and Specht, A. and Grutter, T.} } @article {2011|1889, title = {Impact of Thermostats on Folding and Aggregation Properties of Peptides Using the Optimized Potential for Efficient Structure Prediction Coarse-Grained Model}, journal = {J. Chem. Theory Comput.}, volume = {7}, number = {5}, year = {2011}, month = {may}, pages = {1502{\textendash}1510}, doi = {10.1021/ct100619p}, author = {Spill, Yannick G. and Pasquali, Samuela and Philippe Derreumaux} } @article {2011|1587, title = {Mycoplasma gallisepticum produces a histone-like protein that recognizes base mismatches in DNA}, journal = {Biochemistry}, volume = {50}, year = {2011}, pages = {8692{\textendash}8702}, author = {Dmitri Kamashev and Jacques Oberto and Marina Serebryakova and Alexey Gorbachev and Yulia Zhukova and Sergei Levitskii and Alexey K Mazur and Vadim Govorun} } @article {2011|1738, title = {Non-monotonic dependence of water reorientation dynamics on surface hydrophilicity: competing effects of the hydration structure and hydrogen-bond strength}, journal = {Phys. Chem. Chem. Phys.}, volume = {13}, year = {2011}, pages = {19911}, abstract = {

The reorientation dynamics of interfacial water molecules was recently shown to change non-monotonically next to surfaces of increasing hydrophilicity, with slower dynamics next to strongly hydrophobic (apolar) and very hydrophilic surfaces, and faster dynamics next to surfaces of intermediate hydrophilicities. Through a combination of molecular dynamics simulations and analytic modeling, we provide a molecular interpretation of this behavior. We show that this non-monotonic dependence arises from two competing effects induced by the increasing surface hydrophilicity: first a change in the hydration structure with an enhanced population of water OH bonds pointing toward the surface and second a strengthening of the water-surface interaction energy. The extended jump model, including the effects due to transition-state excluded volume and transition-state hydrogen-bond strength, provides a quasi-quantitative description of the non-monotonic changes in the water reorientation dynamics with surface hydrophilicity.

}, issn = {1463-9076}, author = {Guillaume Stirnemann and Castrillon, Santiago Romero-Vargas and Hynes, James T. and Rossky, Peter J. and Debenedetti, Pablo G. and Laage, Damien} } @article {2011|1487, title = {Real Time Observation of Ultrafast Peptide Conformational Dynamics: Molecular Dynamics Simulation vs Infrared Experiment}, journal = {J. Phys. Chem. B}, volume = {115}, number = {44}, year = {2011}, month = {nov}, pages = {13084{\textendash}13092}, author = {Phuong H. Nguyen and Staudt, Heike and Wachtveitl, Josef and Stock, Gerhard} } @article {2011|1383, title = {Reorientation and Allied Dynamics in Water and Aqueous Solutions}, journal = {Annu. Rev. Phys. Chem.}, volume = {62}, year = {2011}, pages = {395{\textendash}416}, abstract = {

The reorientation of a water molecule is important for a host of phenomena, ranging over?in an only partial listing?the key dynamic hydrogen-bond network restructuring of water itself, aqueous solution chemical reaction mechanisms and rates, ion transport in aqueous solution and membranes, protein folding, and enzymatic activity. This review focuses on water reorientation and related dynamics in pure water, and for aqueous solutes with hydrophobic, hydrophilic, and amphiphilic character, ranging from tetramethylurea to halide ions and amino acids. Attention is given to the application of theory, simulation, and experiment in the probing of these dynamics, in usefully describing them, and in assessing the description. Special emphasis is placed on a novel sudden, large-amplitude jump mechanism for water reorientation, which contrasts with the commonly assumed Debye rotational diffusion mechanism, characterized by small-amplitude angular motion. Some open questions and directions for further research are also discussed. Expected final online publication date for the Annual Review of Physical Chemistry Volume 62 is March 31, 2011. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

}, isbn = {0066-426X 1545-1593}, issn = {0066-426X}, doi = {doi: 10.1146/annurev.physchem.012809.103503}, url = {http://www.annualreviews.org/doi/abs/10.1146/annurev.physchem.012809.103503$\backslash$nhttp://www.annualreviews.org.login.ezproxy.lib.purdue.edu/doi/pdf/10.1146/annurev.physchem.012809.103503}, author = {Laage, Damien and Guillaume Stirnemann and Fabio Sterpone and Rey, Rossend and Hynes, James T.} } @article {2011|1691, title = {On the reorientation and hydrogen-bond dynamics of Alcohols}, journal = {J. Phys. Chem. B}, volume = {115}, year = {2011}, pages = {12173{\textendash}12178}, abstract = {

The mechanism of the OH bond reorientation in liquid methanol and ethanol is examined. It is found that the extended jump model, recently developed for water, describes the OH reorientation in these liquids. The slower reorientational dynamics in these alcohols compared to water can be explained by two key factors. The alkyl groups on the alcohol molecules exclude potential partners for hydrogen bonding exchanges, an effect that grows with the size of the alkyl chain. This increases the importance of the reorientation of intact hydrogen bonds, which also slows with increasing size of the alcohol and becomes the dominant reorientation pathway.

}, issn = {15206106}, author = {Vartia, Anthony A. and Mitchell-Koch, Katie R. and Guillaume Stirnemann and Laage, Damien and Thompson, Ward H.} } @inbook {2011|1773, title = {Role of packing, hydration and fluctuation on Thermostability}, booktitle = {Thermostable Proteins Structural Stability and Design}, year = {2011}, publisher = {CRC Press - Taylor and Francis}, organization = {CRC Press - Taylor and Francis}, author = {Fabio Sterpone and Simone Melchionna}, editor = {Srikanta Sen and Lennart Nilsson} } @article {2011|1474, title = {Simulation of transient infrared spectra of a photoswitchable peptide}, journal = {J. Chem. Phys.}, volume = {135}, number = {12}, year = {2011}, month = {dec}, author = {Kobus, Maja and Lieder, Martin and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2011|1739, title = {Water reorientation dynamics in the first hydration shells of F- and I-}, journal = {Phys. Chem. Chem. Phys.}, volume = {13}, year = {2011}, pages = {19895}, abstract = {

Molecular dynamics and analytic theory results are presented for the reorientation dynamics of first hydration shell water molecules around fluoride and iodide anions. These ions represent the extremes of the (normal) halide series in terms of their size and conventional structure-making and -breaking categorizations. The simulated reorientation times are consistent with NMR and ultrafast IR experimental results. They are also in good agreement with the theoretical predictions of the analytic Extended Jump Model. Analysis through this model shows that while sudden, large amplitude jumps (in which the reorienting water exchanges hydrogen-bond partners) are the dominant reorientation pathway for the I(-) case, they are comparatively less important for the F(-) case. In particular, the diffusive reorientation of an intact F(-)...H(2)O hydrogen-bonded pair is found to be most important for the reorientation time, a feature related to the greater hydrogen-bond strength for the F(-)...H(2)O pair. The dominance of this effect for e.g. multiply charged ions is suggested.

}, issn = {1463-9076}, author = {Boisson, Jean and Guillaume Stirnemann and Laage, Damien and Hynes, James T.} } @article {2011|1505, title = {X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel}, journal = {Nature}, volume = {469}, year = {2011}, month = {jan}, pages = {428{\textendash}431}, keywords = {anaesthetics, desflurane, GLIC, propofol}, url = {http://www.nature.com/nature/journal/v469/n7330/full/nature09647.html}, author = {H. Nury and C. Van Renterghem and Y. Weng and A. Tran and Marc Baaden and V. Dufresne and J.-P. Changeux and J. M. Sonner and M. Delarue and P.-J. Corringer} } @article {2010|1696, title = {Direct evidence of angular jumps during water reorientation through two-dimensional infrared anisotropy}, journal = {J. Phys. Chem. Lett.}, volume = {1}, year = {2010}, pages = {1511{\textendash}1516}, abstract = {

Water reorientation was recently suggested via simulations to proceed through large angular jumps, but direct experimental evidence has so far remained elusive. Here we show that both infrared pump-probe and photon echo spectroscopies can provide such evidence through the measurement of the two-dimensional anisotropy decay. We calculate these two-dimensional anisotropies from simulations and show they can be interpreted as a vibrational frequency-dependent resolved orientation time-correlation function. We develop a frequency-dependent extended jump model to predict the nature of the angular jump signature in these anisotropies. This model provides a rigorous and unambiguous connection between ultrafast infrared experimental results and the presence of angular jumps in bulk water, and calls for new experiments.

}, issn = {19487185}, doi = {10.1021/jz100385r}, author = {Guillaume Stirnemann and Laage, Damien} } @article {2010|1613, title = {Functional Modes and Residue Flexibility Control the Anisotropic Response of Guanylate Kinase to Mechanical Stress}, journal = {Biophys. J.}, volume = {99}, number = {10}, year = {2010}, pages = {3412{\textendash}3419}, doi = {10.1016/j.bpj.2010.09.026}, author = {S Sacquin-Mora and Delalande, O. and Marc Baaden} } @article {2010|1788, title = {How does heparin prevent the p{H} inactivation of cathepsin {B}? Allosteric mechanism elucidated by docking and molecular dynamics.}, journal = {Bmc Genomics}, volume = {11, S5}, year = {2010}, author = {Mauricio G.S. Costa and Paulo R. Batista and Cl{\`a}udio S Shida and Charles H. Robert and Paulo M. Bisch and Pedro G. Pascutti} } @article {2010|1470, title = {Infrared signatures of the peptide dynamical transition: A molecular dynamics simulation study}, journal = {J. Chem. Phys.}, volume = {133}, number = {3}, year = {2010}, month = {jul}, author = {Kobus, Maja and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2010|1512, title = {{M}odeling the early stage of {D}{N}{A} sequence recognition within {R}ec{A} nucleoprotein filaments}, journal = {Nucleic Acids Res.}, volume = {38}, year = {2010}, month = {oct}, pages = {6313{\textendash}6323}, author = {A Saladin and Amourda, C. and Poulain, P. and Nicolas F{\'e}rey and Marc Baaden and Martin Zacharias and Delalande, O. and Chantal Pr{\'e}vost} } @inbook {2010|1569, title = {Molecular dynamics studies of outer membrane proteins : a story of barrels}, year = {2010}, pages = {225{\textendash}247}, publisher = {Royal Society of Chemistry}, organization = {Royal Society of Chemistry}, chapter = {Molecular Simulations and Biomembranes: From Biophysics to Function}, address = {United Kingdom}, author = {S. Khalid and Marc Baaden}, editor = {P.C. Biggin and M.S.P. Sansom} } @article {2010|1685, title = {Non adiabatic simulations of exciton dissociation in poly-p-phenylenevinylene oligomers}, journal = {J. Phys. Chem. A}, volume = {114}, year = {2010}, pages = {7661{\textendash}7670}, author = {M. Bedard-Hearn and Fabio Sterpone and P.J. Rossky} } @article {2010|1472, title = {Nonequilibrium molecular dynamics simulation of the energy transport through a peptide helix}, journal = {J. Chem. Phys.}, volume = {132}, number = {2}, year = {2010}, month = {jan}, author = {Phuong Hoang Nguyen and Park, Sang-Min and Stock, Gerhard} } @article {2010|1395, title = {{P}hotocontrol of protein activity in cultured cells and zebrafish with one- and two-photon illumination}, journal = {Chembiochem}, volume = {11}, year = {2010}, month = {mar}, pages = {653{\textendash}663}, author = {Sinha, D. K. and Neveu, P. and Gagey, N. and Aujard, I. and Benbrahim-Bouzidi, C. and Le Saux, T. and Rampon, C. and Gauron, C. and Goetz, B. and Dubruille, S. and Marc Baaden and Volovitch, M. and Bensimon, D. and Vriz, S. and Jullien, L.} } @inbook {2010|1758, title = {Protein-Protein Docking}, booktitle = {Protein-Protein Complexes. Analysis, Modeling and Drug Design}, year = {2010}, pages = {147{\textendash}181}, publisher = {Imperial College Press}, organization = {Imperial College Press}, chapter = {6}, author = {A Saladin and Chantal Pr{\'e}vost}, editor = {Martin Zacharias} } @article {2010|1789, title = {Single-spanning transmembrane domains in cell growth and cell-cell interactions: More than meets the eye?}, journal = {Cell Adh. Migr.}, volume = {4}, number = {2}, year = {2010}, month = {apr}, pages = {313{\textendash}324}, abstract = {

As a whole, integral membrane proteins represent about one third of sequenced genomes, and more than 50\% of currently available drugs target membrane proteins, often cell surface receptors. Some membrane protein classes, with a defined number of transmembrane (TM) helices, are receiving much attention because of their great functional and pharmacological importance, such as G protein-coupled receptors possessing 7 TM segments. Although they represent roughly half of all membrane proteins, bitopic proteins (with only 1 TM helix) have so far been less well characterized. Though they include many essential families of receptors, such as adhesion molecules and receptor tyrosine kinases, many of which are excellent targets for biopharmaceuticals (peptides, antibodies, et al.). A growing body of evidence suggests a major role for interactions between TM domains of these receptors in signaling, through homo and heteromeric associations, conformational changes, assembly of signaling platforms, etc. Significantly, mutations within single domains are frequent in human disease, such as cancer or developmental disorders. This review attempts to give an overview of current knowledge about these interactions, from structural data to therapeutic perspectives, focusing on bitopic proteins involved in cell signaling.

}, keywords = {Animals, Biological, Humans, Membrane Proteins, Models, Protein Structure, Secondary, Signal Transduction, Tertiary}, issn = {1933-6926}, doi = {10.4161/cam.4.2.12430}, author = {Pierre Hubert and Paul Sawma and Jean-Pierre Duneau and Jonathan Khao and J{\'e}r{\^o}me H{\'e}nin and Dominique Bagnard and James Sturgis} } @article {2010|1444, title = {{T}he molecular recognition mechanism for superoxide dismutase presequence binding to the mitochondrial protein import receptor {T}om20 from {O}ryza sativa involves an {L}{R}{T}{L}{A} motif}, journal = {J. Phys. Chem. B}, volume = {114}, year = {2010}, month = {nov}, pages = {13839{\textendash}13846}, author = {Y. Zhang and Marc Baaden and J. Yan and J. Shao and S. Qiu and Y. Wu and Y. Ding} } @article {2010|1445, title = {Water around thermophilic proteins: the role of charged and apolar atoms}, journal = {J Phys: Cond Matt}, volume = {22}, number = {28}, year = {2010}, pages = {284113}, author = {Fabio Sterpone and Claudia Bertonati and Giuseppe Briganti and Simone Melchionna} } @article {2010|1692, title = {Water hydrogen bond dynamics in aqueous solutions of amphiphiles}, journal = {J. Phys. Chem. B}, volume = {114}, year = {2010}, pages = {3052{\textendash}3059}, abstract = {

The hydrogen bond dynamics of water in a series of amphiphilic solute solutions are investigated through simulations and analytic modeling with an emphasis on the interpretation of experimentally accessible two-dimensional infrared (2D IR) photon echo spectra. We evidence that for most solutes the major effect in the hydration dynamics comes from the hydrophilic groups. These groups can retard the water dynamics much more significantly than can hydrophobic groups by forming strong hydrogen bonds with water. By contrast, hydrophobic groups are shown to have a very moderate effect on water hydrogen bond breaking kinetics. We also present the first calculation of the 2D IR spectra for these solutions. While 2D IR spectroscopy is a powerful technique to probe water hydrogen bond network fluctuations, interpretations of aqueous solution spectra remain ambiguous. We show that a complementary approach through simulations and calculation of the spectra lifts the ambiguity and provides a clear connection between the simulated molecular picture and the experimental spectroscopy data. For amphiphilic solute solutions, we show that, in contrast with techniques such as NMR or ultrafast anisotropy, 2D IR spectroscopy can discriminate between waters next to the solutes hydrophobic and hydrophilic groups. We also evidence that the water dynamics slowdown due to the hydrophilic groups is dramatically enhanced in the 2D IR spectral relaxation, because these groups can induce a slow chemical exchange with the bulk, even when recognized exchange signatures are absent. Implications for the understanding of water around chemically heterogeneous systems such as protein surfaces and for the interpretation of 2D IR spectra in these cases are discussed.

}, issn = {15206106}, author = {Guillaume Stirnemann and Hynes, James T. and Laage, Damien} } @article {2010|1832, title = {Water hydrogen-bond dynamics around amino acids: the key role of hydrophilic hydrogen-bond acceptor groups}, journal = {J. Phys. Chem. B}, volume = {114}, number = {5}, year = {2010}, pages = {2083{\textendash}9}, abstract = {

Water hydrogen-bond (HB) dynamics around amino acids in dilute aqueous solution is investigated through molecular dynamics simulations and analytic modeling. We especially highlight the critical role played by hydrophilic HB acceptors: the strength of the HB formed with water has a pronounced effect on the HB dynamics, in accord with several experimental observations. In contrast, we evidence that hydrophilic HB donors induce a moderate slowdown in the water HB exchange dynamics due to an excluded volume effect, similar to that of hydrophobic groups. We present an analytic model which rationalizes the effect of all examined amino acid sites on the HB dynamics and whose predictions are in excellent agreement with the numerical simulations. This model provides the acceleration or retardation in the HB exchange time with respect to the bulk through the combination of the solute excluded volume factor with the solute-water HB strength factor, both referring to the HB exchange transition state.

}, author = {Sterpone, Fabio and Guillaume Stirnemann and Hynes, James T and Laage, Damien} } @article {2010|1649, title = {Water reorientation, hydrogen-bond dynamics and 2D-IR spectroscopy next to an extended hydrophobic surface.}, journal = {Farad. Discuss.}, volume = {146}, year = {2010}, pages = {263{\textendash}281}, abstract = {

The dynamics of water next to hydrophobic groups is critical for several fundamental biochemical processes such as protein folding and amyloid fiber aggregation. Some biomolecular systems, like melittin or other membrane-associated proteins, exhibit extended hydrophobic surfaces. Due to the strain these surfaces impose on the hydrogen (H)-bond network, the water molecules shift from the clathrate-like arrangement observed around small solutes to an anticlathrate-like geometry with some dangling OH bonds pointing toward the surface. Here we examine the water reorientation dynamics next to a model hydrophobic surface through molecular dynamics simulations and analytic modeling. We show that the water OH bonds lying next to the hydrophobic surface fall into two subensembles with distinct dynamical reorientation properties. The first is the OH bonds tangent to the surface; these exhibit a behavior similar to the water OHs around small hydrophobic solutes, i.e. with a moderate reorientational slowdown explained by an excluded volume effect due to the surface. The second is the dangling OHs pointing toward the surface: these are not engaged in any H-bond, reorient much faster than in the bulk, and exhibit an unusual anisotropy decay which becomes negative for delays of a few picoseconds. The H-bond dynamics, i.e. the exchanges between the different configurations, and the resulting anisotropy decays are analyzed within the analytic extended jump model. We also show that a recent spectroscopy technique, two-dimensional time resolved vibrational spectroscopy (2D-IR), can be used to selectively follow the dynamics of dangling OHs, since these are spectrally distinct from H-bonded ones. By computing the first 2D-IR spectra of water next to a hydrophobic surface, we establish a connection between the spectral dynamics and the dynamical properties that we obtain directly from the simulations.

}, issn = {1359-6640}, author = {Guillaume Stirnemann and Rossky, Peter J and Hynes, James T and Laage, Damien} } @article {2009|1442, title = {{C}harge {R}ecombination {K}inetics and {P}rotein {D}ynamics in {W}ild {T}ype and {C}arotenoid-less {B}acterial {R}eaction {C}enters: {S}tudies in {T}rehalose {G}lasses}, journal = {J. Phys. Chem. B}, volume = {113}, year = {2009}, month = {jul}, pages = {10389{\textendash}1398}, author = {Francia, F. and Malferrari, M. and S Sacquin-Mora and Venturoli, G.} } @article {2009|1399, title = {{C}oarse-grain simulations of the {R}-{S}{N}{A}{R}{E} fusion protein in its membrane environment detect long-lived conformational sub-states}, journal = {Chemphyschem}, volume = {10}, year = {2009}, month = {jul}, pages = {1548{\textendash}1552}, author = {Durrieu, M. P. and Bond, P. J. and Sansom, M. S. and Lavery, R. and Marc Baaden} } @book {2009|1567, title = {Coarse-graining protein mechanics}, volume = {Coarse-Graining of Condensed Phase and Biomolecular Systems}, year = {2009}, publisher = {Taylor and Francis}, organization = {Taylor and Francis}, author = {R Lavery and S Sacquin-Mora}, editor = {G. Voth} } @article {2009|2018, title = {Energy Flow and Long-Range Correlations in Guanine-Binding Riboswitch: A Nonequilibrium Molecular Dynamics Study}, journal = {J. Phys. Chem. B}, volume = {113}, number = {27}, year = {2009}, month = {jul}, pages = {9340{\textendash}9347}, keywords = {Binding Sites, Computer Simulation, Energy Transfer, Guanine, Ligands, Models, Molecular, Nucleic Acid Conformation, RNA, Temperature}, doi = {10.1021/jp902013s}, author = {Phuong Hoang Nguyen and Philippe Derreumaux and Stock, Gerhard} } @article {2009|1486, title = {Free-Energy Landscape of RNA Hairpins Constructed via Dihedral Angle Principal Component Analysis}, journal = {J. Phys. Chem. B}, volume = {113}, number = {52}, year = {2009}, month = {dec}, pages = {16660{\textendash}16668}, author = {Riccardi, Laura and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2009|1605, title = {The HSP90 binding mode of a radicicol-like E-oxime determined by docking, binding free energy estimations, and NMR 15 N chemical shifts}, journal = {Biophys. Chem.}, volume = {143}, number = {3}, year = {2009}, pages = {111{\textendash}123}, publisher = {Elsevier}, author = {Spichty, Martin and Antoine Taly and Hagn, Franz and Kessler, Horst and Barluenga, Sofia and Winssinger, Nicolas and Karplus, Martin} } @article {2009|1959, title = {Joint Evolutionary Trees: A Large-Scale Method To Predict Protein Interfaces Based on Sequence Sampling}, journal = {Plos Comput. Biol.}, volume = {5}, number = {1}, year = {2009}, month = {jan}, pages = {e1000267}, doi = {10.1371/journal.pcbi.1000267}, url = {http://dx.doi.org/10.1371\%2Fjournal.pcbi.1000267}, author = {Engelen, Stefan and Trojan, Ladislas A. and S Sacquin-Mora and Lavery, Richard and Carbone, Alessandra} } @article {2009|1831, title = {Key role of proximal water in regulating thermostable proteins}, journal = {J. Phys. Chem. B}, volume = {113}, number = {1}, year = {2009}, month = {jan}, pages = {131{\textendash}7}, abstract = {Three homologous proteins with mesophilic, thermophilic and hyperthermophilic character have been studied via molecular dynamics simulations at four different temperatures in order to investigate how water controls thermostability. The water-exposed surface of the protein is shown to increase with the degree of thermophilicity, and the role of water in enhancing the protein internal flexibility and structural robustness is elucidated. The presence of water-water hydrogen bond clusters enveloping the macromolecule is shown to correlate with thermal robustness when going from the mesophilic to the hyperthermophilic variants. Our analysis indicates that essential contributions to thermostability stem from protein-water surface effects whereas the protein internal packing plays a minor role.}, doi = {10.1021/jp805199c}, author = {Sterpone, Fabio and Bertonati, Claudia and Briganti, Giuseppe and Melchionna, Simone} } @article {2009|1799, title = {{M}odeling the {M}echanical {R}esponse of {P}roteins to {A}nisotropic {D}eformation}, journal = {Chemphyschem}, volume = {10}, number = {1}, year = {2009}, month = {jan}, pages = {115{\textendash}118}, doi = {10.1002/cphc.200800480}, author = {S Sacquin-Mora and Lavery, R.} } @article {2009|1864, title = {Models for phosphatidylglycerol lipids put to a structural test}, journal = {J. Phys. Chem. B}, volume = {113}, number = {19}, year = {2009}, pages = {6958{\textendash}6963}, publisher = {Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA. jhenin@cmm.chem.upenn.edu}, abstract = {Three atomistic empirical models for phosphatidylglycerol (PG) lipids are tested against structural data in the crystal and liquid crystal states. Simulations of the anhydrous crystal of dimyristoyl-phosphatidylglycerol (DMPG) show that only the CHARMM force field describes the conformation and interactions of PG head groups accurately. The other two models do not reproduce the native network of hydrogen bonds, suggesting the presence of biases in their conformational and nonbonded interaction properties. The CHARMM model is further validated in the biologically relevant liquid crystal phase by comparing experimental small-angle X-ray scattering spectra from DMPG unilamellar vesicles with data calculated from fluid bilayer simulations. The good agreement found in this model-free comparison implies that liquid crystal PG bilayers as described by CHARMM exhibit realistic bilayer thickness and lateral packing. Last, this model is used to simulate a fluid bilayer of palmitoyl-oleoyl-phosphatidylglycerol (POPG). The resulting view of the POPG bilayer structure is at variance with that proposed previously based on simulations, in particular, with respect to lateral packing of head groups and the role of counterions.}, keywords = {chemistry, Crystallography, Lipid Bilayers, Models, Molecular, Phosphatidylglycerols, Scattering, Small Angle, Water, X-Ray}, doi = {10.1021/jp900645z}, author = {J{\'e}r{\^o}me H{\'e}nin and Wataru Shinoda and Michael L Klein} } @article {2009|1469, title = {Molecular dynamics simulation of cooling: Heat transfer from a photoexcited peptide to the solvent}, journal = {J. Chem. Phys.}, volume = {131}, number = {18}, year = {2009}, month = {nov}, author = {Park, Sang-Min and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2009|1440, title = {Nonadiabatic mixed quantum-classical dynamic simulation of pi-stacked oligophenylenevinylenes}, journal = {J. Phys. Chem. A}, volume = {113}, number = {15}, year = {2009}, pages = {3427{\textendash}30}, author = {Sterpone, Fabio and Bedard-Hearn, Michael J and Rossky, Peter J} } @inbook {2009|1568, title = {Nonequilibrium molecular dynamics simulation of photoinduced energy flow in peptides: theory meets experiment}, year = {2009}, publisher = {CRC Press}, organization = {CRC Press}, author = {Phuong Hoang Nguyen and P. Hamm and G. Stock}, editor = {D. Leitner and J. Straub} } @article {2009|1392, title = {{PT}ools: an opensource molecular docking library.}, journal = {Bmc Struct. Biol.}, volume = {9}, year = {2009}, pages = {27{\textendash}37}, doi = {10.1186/1472-6807-9-27}, author = {A Saladin and Fiorucci, S and Poulain, P and Chantal Pr{\'e}vost and Martin Zacharias} } @article {2009|1443, title = {{R}elating the {D}iffusion of {S}mall {L}igands in {H}uman {N}euroglobin to {I}ts {S}tructural and {M}echanical {P}roperties}, journal = {J. Phys. Chem. B}, volume = {113}, number = {50}, year = {2009}, month = {nov}, pages = {16257{\textendash}16267}, author = {Bocahut, A. and Bernad, S. and Sebban, P. and S Sacquin-Mora} } @article {2009|1495, title = {Sphere versus cylinder: the effect of packing on the structure of nonionic C12E6 micelles}, journal = {Langmuir}, volume = {25}, number = {16}, year = {2009}, pages = {8960{\textendash}7}, author = {Sterpone, Fabio and Briganti, G and Pierleoni, C} } @article {2009|1693, title = {Why water reorientation slows without iceberg formation around hydrophobic solutes}, journal = {J. Phys. Chem. B}, volume = {113}, year = {2009}, pages = {2428{\textendash}2435}, abstract = {

The dynamics of water molecules next to hydrophobic solutes is investigated, specifically addressing the recent controversy raised by the first time-resolved observations, which concluded that some water molecules are immobilized by hydrophobic groups, in strong contrast to previous NMR conclusions. Through molecular dynamics simulations and an analytic jump reorientation model, we identify the water reorientation mechanism next to a hydrophobic solute and provide evidence that no water molecules are immobilized by hydrophobic solutes. Their moderate rotational slowdown compared to bulk water (e.g., by a factor of less than 2 at low solute concentration) is mainly due to slower hydrogen-bond exchange. The slowdown is quantitatively described by a solute excluded volume effect at the transition state for the key hydrogen-bond exchange in the reorientation mechanism. We show that this picture is consistent with both ultrafast anisotropy and NMR experimental results and that the transition state excluded volume theory yields quantitative predictions of the rotational slowdown for diverse hydrophobic solutes of varying size over a wide concentration range. We also explain why hydrophobic groups slow water reorientation less than do some hydrophilic groups.

}, author = {Laage, Damien and Guillaume Stirnemann and Hynes, James T.} } @article {2008|1583, title = {{C}omparative models of {P}2{X}2 receptor support inter-subunit {A}{T}{P}-binding sites}, journal = {Biochem. Biophys. Res. Commun.}, volume = {375}, number = {3}, year = {2008}, month = {oct}, pages = {405{\textendash}409}, author = {Guerlet, G. and Antoine Taly and Prado de Carvalho, L. and Martz, A. and Jiang, R. and Specht, A. and Le Novere, N. and Grutter, T.} } @article {2008|1585, title = {Comparative models of P2X2 receptor support inter-subunit ATP-binding sites}, journal = {Biochem. Biophys. Res. Commun.}, volume = {375}, number = {3}, year = {2008}, pages = {405{\textendash}409}, publisher = {Academic Press}, author = {Guerlet, Guillaume and Antoine Taly and De Carvalho, Lia Prado and Martz, Adeline and Jiang, Ruotian and Specht, Alexandre and Le Novere, Nicolas and Grutter, Thomas} } @article {2008|1884, title = {The complex folding pathways of protein A suggest a multiple-funnelled energy landscape}, journal = {J. Chem. Phys.}, volume = {128}, number = {4}, year = {2008}, month = {jan}, pages = {045101}, doi = {10.1063/1.2812562}, author = {St-Pierre, Jean-Francois and Mousseau, Normand and Philippe Derreumaux} } @article {2008|1468, title = {Construction of the free energy landscape of biomolecules via dihedral angle principal component analysis}, journal = {J. Chem. Phys.}, volume = {128}, number = {24}, year = {2008}, month = {jun}, author = {Altis, Alexandros and Otten, Moritz and Phuong Hoang Nguyen and Hegger, Rainer and Stock, Gerhard} } @article {2008|1603, title = {Diffusion of glycerol through Escherichia coli aquaglyceroporin GlpF}, journal = {Biophys. J.}, volume = {94}, number = {3}, year = {2008}, pages = {832{\textendash}839}, abstract = {The glycerol uptake facilitator, GlpF, a major intrinsic protein found in Escherichia coli, selectively conducts water and glycerol across the inner membrane. The free energy landscape characterizing the assisted transport of glycerol by this homotetrameric aquaglyceroporin has been explored by means of equilibrium molecular dynamics over a timescale spanning 0.12 micros. To overcome the free energy barriers of the conduction pathway, an adaptive biasing force is applied to the glycerol molecule confined in each of the four channels. The results illuminate the critical role played by intramolecular relaxation on the diffusion properties of the permeant. These free energy calculations reveal that glycerol tumbles and isomerizes on a timescale comparable to that spanned by its adaptive-biasing-force-assisted conduction in GlpF. As a result, reorientation and conformational equilibrium of glycerol in GlpF constitute a bottleneck in the molecular simulations of the permeation event. A profile characterizing the position-dependent diffusion of the permeant has been determined, allowing reaction rate theory to be applied for investigating conduction kinetics based on the measured free energy landscape.}, keywords = {Aquaporins, Chemical, Computer Simulation, Diffusion, Escherichia coli Proteins, Glycerol, Ion Channel Gating, Models, Molecular, Molecular Conformation, Porosity}, doi = {10.1529/biophysj.107.115105}, author = {J{\'e}r{\^o}me H{\'e}nin and Emad Tajkhorshid and Klaus Schulten and Christophe Chipot} } @article {2008|1434, title = {Dissecting the Hydrogen Bond: A Quantum Monte Carlo Approach}, journal = {J Chem Theo Comp}, volume = {4}, number = {9}, year = {2008}, pages = {1428{\textendash}1434}, author = {Sterpone, Fabio and Spanu, Leonardo and Ferraro, Luca and Sorella, Sandro and Guidoni, Leonardo} } @article {2008|1695, title = {Does water condense in hydrophobic cavities? A molecular simulation study of hydration in heterogeneous nanopores}, journal = {J. Phys. Chem. C}, volume = {112}, year = {2008}, pages = {10435{\textendash}10445}, author = {Cailliez, Fabien and Guillaume Stirnemann and Boutin, Anne and Demachy, Isabelle and Fuchs, Alain H.} } @article {2008|1485, title = {Energy transport in peptide helices: A comparison between high- and low-energy excitations}, journal = {J. Phys. Chem. B}, volume = {112}, number = {30}, year = {2008}, month = {jul}, pages = {9091{\textendash}9099}, author = {Backus, Ellen H. G. and Phuong Hoang Nguyen and Botan, Virgiliu and Pfister, Rolf and Moretto, Alessandro and Crisma, Marco and Toniolo, Claudio and Stock, Gerhard and Hamm, Peter} } @article {2008|1710, title = {Identification of Protein Interaction Partners and Protein-Protein Interaction Sites}, journal = {J. Mol. Biol.}, volume = {382}, number = {5}, year = {2008}, pages = {1276{\textendash}1289}, doi = {10.1016/j.jmb.2008.08.002}, author = {S Sacquin-Mora and Carbone, A. and Richard Lavery} } @article {2008|1662, title = {Insights on protein-DNA recognition by coarse grain modelling}, journal = {J. Comput. Chem.}, volume = {29}, year = {2008}, month = {nov}, pages = {2582{\textendash}92}, abstract = {

Coarse grain modelling of macromolecules is a new approach, potentially well adapted to answer numerous issues, ranging from physics to biology. We propose here an original DNA coarse grain model specifically dedicated to protein-DNA docking, a crucial, but still largely unresolved, question in molecular biology. Using a representative set of protein-DNA complexes, we first show that our model is able to predict the interaction surface between the macromolecular partners taken in their bound form. In a second part, the impact of the DNA sequence and electrostatics, together with the DNA and protein conformations on docking is investigated. Our results strongly suggest that the overall DNA structure mainly contributes in discriminating the interaction site on cognate proteins. Direct electrostatic interactions between phosphate groups and amino acid side chains strengthen the binding. Overall, this work demonstrates that coarse grain modeling can reveal itself a precious auxiliary for a general and complete description and understanding of protein-DNA association mechanisms.

}, doi = {10.1002/jcc.21014}, author = {Poulain, P and A Saladin and Hartmann, B and Chantal Pr{\'e}vost} } @article {2008|1829, title = {Molecular modeling and simulation of conjugated polymer oligomers: ground and excited state chain dynamics of PPV in the gas phase}, journal = {J. Phys. Chem. B}, volume = {112}, number = {16}, year = {2008}, pages = {4983{\textendash}93}, author = {Sterpone, Fabio and Rossky, Peter J} } @article {2008|1480, title = {Multiple-step virtual screening using VSM-G: Overview and validation of fast geometrical matching enrichment}, journal = {J. Mol. Model.}, volume = {14}, number = {5}, year = {2008}, pages = {393{\textendash}401}, author = {A Beautrait and V Leroux and Matthieu Chavent and L Ghemtio and M.-D Devignes and M Smail-Tabbone and W Cai and X Shao and G Moreau and P Bladon and J Yao and B Maigret} } @article {2008|1397, title = {Nonadiabatic vibrational dynamics and spectroscopy of peptides: A quantum-classical description}, journal = {Chem. Phys.}, volume = {347}, number = {1-3}, year = {2008}, month = {may}, pages = {208{\textendash}217}, author = {Kobus, Maja and Gorbunov, Roman D. and Phuong Hoang Nguyen and Stock, Gerhard} } @inbook {2008|1566, title = {Order-disorder transitions in ribosome assembly}, booktitle = {Ribosomal proteins,}, year = {2008}, publisher = {Nova publishers, Hauppauge NY}, organization = {Nova publishers, Hauppauge NY}, author = {Y Timsit and F Allemand and Chiaruttini C and M Springer}, editor = {Colombus} } @article {2008|1409, title = {Outer membrane proteins: comparing X-ray and NMR structures by MD simulations in lipid bilayers}, journal = {European Biophysics Journal with Biophysics Letters}, volume = {37}, number = {2}, year = {2008}, month = {feb}, pages = {131{\textendash}141}, author = {Cox, Katherine and Bond, Peter J. and Grottesi, Alessandro and Marc Baaden and Sansom, Mark S. P.} } @article {2008|1494, title = {Pressure-induced core packing and interfacial dehydration in nonionic C12E6 micelle in aqueous solution}, journal = {Langmuir}, volume = {24}, number = {12}, year = {2008}, pages = {6067{\textendash}71}, author = {Sterpone, Fabio and Briganti, G and Melchionna, S and Pierleoni, C} } @article {2008|1812, title = {Self-assembly of amyloid-forming peptides by molecular dynamics simulations}, journal = {Front. Biosci.}, volume = {13}, year = {2008}, month = {may}, pages = {5681{\textendash}5692}, author = {Wei, Guanghong and Song, Wei and Philippe Derreumaux and Mousseau, Normand} } @article {2008|1915, title = {Self-assembly of the beta 2-microglobulin NHVTLSQ peptide using a coarse-grained protein model reveals beta-barrel species}, journal = {J. Phys. Chem. B}, volume = {112}, number = {14}, year = {2008}, month = {apr}, pages = {4410{\textendash}4418}, doi = {10.1021/jp710592v}, author = {Song, Wei and Wei, Guanghong and Mousseau, Normand and Philippe Derreumaux} } @article {2008|1484, title = {Structural Flexibility of a Helical Peptide Regulates Vibrational Energy Transport Properties}, journal = {J. Phys. Chem. B}, volume = {112}, number = {48}, year = {2008}, month = {dec}, pages = {15487{\textendash}15492}, author = {Backus, Ellen H. G. and Phuong Hoang Nguyen and Botan, Virgiliu and Moretto, Alessandro and Crisma, Marco and Toniolo, Claudio and Zerbe, Oliver and Stock, Gerhard and Hamm, Peter} } @article {2008|1866, title = {United-Atom Acyl Chains for {CHARMM} Phospholipids}, journal = {J. Phys. Chem. B.}, volume = {112}, number = {23}, year = {2008}, pages = {7008{\textendash}7015}, publisher = {Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, Pennsylvania 19104-6323, and Research Institute for Computational Sciences, National Institute of Advanced Industrial Science and Technol}, abstract = {In all-atom simulations of lipid membranes, explicit hydrogen atoms contained in the hydrocarbon region are described by a large number of degrees of freedom, although they convey only limited physical information. We propose an implicit-hydrogen model for saturated and monounsaturated acyl chains, aimed at complementing the all-atom CHARMM27 model for phospholipid headgroups. Torsional potentials and nonbonded parameters were fitted to reproduce experimental data and free energy surfaces of all-atom model systems. Comparative simulations of fluid-phase POPC bilayers were performed using the all-hydrogen force field and the present model. The hybrid model accelerates a typical bilayer simulation by about 50\% while sacrificing a minimal amount of detail with respect to the fully atomistic description. In addition, the united-atom description is energetically compatible with all-atom CHARMM models, making it suitable for simulations of complex membrane systems.}, doi = {10.1021/jp800687p}, author = {J{\'e}r{\^o}me H{\'e}nin and Wataru Shinoda and Michael L Klein} } @article {2008|1678, title = {Water-water hydrogen bond studied by QMC}, journal = {J. Chem. Theory. Comput.}, volume = {4}, year = {2008}, pages = {1428{\textendash}1432}, author = {Fabio Sterpone and L. Spanu and L. Ferraro and S. Sorella and L. Guidoni} } @conference {2007|1517, title = {Atomistic modeling of the membrane-embedded synaptic fusion complex: a grand challenge project on the DEISA HPC infrastructure}, booktitle = {ParCo 2007, Parallel Computing: Architectures, Algorithms and Applications}, volume = {38}, year = {2007}, pages = {729{\textendash}736}, publisher = {John von Neumann Institute for Computing, Juelich, Germany.}, organization = {John von Neumann Institute for Computing, Juelich, Germany.}, url = {http://www.booksonline.iospress.nl/Content/View.aspx?piid=8468}, author = {E. Krieger and L. Leger and M.P. Durrieu and N. Taib and P. Bond and M. Laguerre and R. Lavery and M.S.P. Sansom and Marc Baaden}, editor = {C.B.G.R. Joubert and F. Peters and T. Lippert and M. Buecker and B. Gibbon and and B. Mohr} } @article {2007, title = {Dihedral angle principal component analysis of molecular dynamics simulations}, journal = {J. Chem. Phys.}, volume = {126}, number = {24}, year = {2007}, month = {jun}, author = {Altis, Alexandros and Phuong Hoang Nguyen and Hegger, Rainer and Stock, Gerhard} } @article {2007|1534, title = {Energy transport in peptide helices}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {104}, number = {31}, year = {2007}, month = {jul}, pages = {12749{\textendash}12754}, author = {Botan, Virgiliu and Backus, Ellen H. G. and Pfister, Rolf and Moretto, Alessandro and Crisma, Marco and Toniolo, Claudio and Phuong Hoang Nguyen and Stock, Gerhard and Hamm, Peter} } @article {2007|1522, title = {How complex is the dynamics of peptide folding?}, journal = {Phys. Rev. Lett.}, volume = {98}, number = {2}, year = {2007}, month = {jan}, author = {Hegger, Rainer and Altis, Alexandros and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2007|1828, title = {How protein surfaces induce anomalous dynamics of hydration water}, journal = {J. Phys. Chem. B}, volume = {111}, number = {26}, year = {2007}, pages = {7584{\textendash}90}, abstract = {Water around biomolecules slows down with respect to pure water, and both rotation and translation exhibit anomalous time dependence in the hydration shell. The origin of such behavior remains elusive. We use molecular dynamics simulations of water dynamics around several designed protein models to establish the connection between the appearance of the anomalous dynamics and water-protein interactions. For the first time we quantify the separate effect of protein topological and energetic disorder on the hydration water dynamics. When a static protein structure is simulated, we show that both types of disorder contribute to slow down water diffusion, and that allowing for protein motion, increasing the spatial dimensionality of the interface, reduces the anomalous character of hydration water. The rotation of water is, instead, altered by the energetic disorder only; indeed, when electrostatic interactions between the protein and water are switched off, water reorients even faster than in the bulk. The dynamics of water is also related to the collective structure{\textendash}{\`a} voir the hydrogen bond (H-bond) network{\textendash}formed by the solvent enclosing the protein surface. We show that, as expected for a full hydrated protein, when the protein surface offers pinning sites (charged or polar sites), the superficial water-water H-bond network percolates throughout the whole surface, hindering the water diffusion, whereas it does not when the protein surface lacks electrostatic interactions with water and the water diffusion is enhanced.}, author = {Pizzitutti, Francesco and Marchi, Massimo and Sterpone, Fabio and Rossky, Peter J} } @article {2007|1984, title = {Locating the active sites of enzymes using mechanical properties}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {67}, number = {2}, year = {2007}, month = {may}, pages = {350{\textendash}359}, doi = {10.1002/prot.21353}, author = {S Sacquin-Mora and Laforet, Emilie and Lavery, Richard} } @article {2007|1535, title = {Monomer adds to preformed structured oligomers of A beta-peptides by a two-stage dock-lock mechanism}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {104}, number = {1}, year = {2007}, month = {jan}, pages = {111{\textendash}116}, author = {Phuong Hoang Nguyen and Li, Mai Suan and Stock, Gerhard and Straub, John E. and Thirumalai, D.} } @article {2007|1588, title = {Probing the flexibility of the bacterial reaction center: The wild-type protein is more rigid than two site-specific mutants}, journal = {Biochemistry}, volume = {46}, number = {51}, year = {2007}, month = {dec}, pages = {14960{\textendash}14968}, doi = {10.1021/bi7004416}, author = {S Sacquin-Mora and Sebban, P. and Derrien, V. and Frick, B. and Richard Lavery and Alba-Simionesco, C.} } @article {2007|1868, title = {Protein mechanics: a route from structure to function}, journal = {Journal of Biosciences}, volume = {32}, number = {5, Sp. Iss. SI}, year = {2007}, month = {aug}, pages = {891{\textendash}898}, doi = {10.1007/s12038-007-0089-x}, author = {Lavery, Richard and S Sacquin-Mora} } @article {2007|1467, title = {Quantum-classical description of the amide I vibrational spectrum of trialanine}, journal = {J. Chem. Phys.}, volume = {126}, number = {5}, year = {2007}, month = {feb}, author = {Gorbunov, Roman D. and Phuong Hoang Nguyen and Kobus, Maja and Stock, Gerhard} } @article {2007|1489, title = {Structure and dynamics of the homologous series of alanine peptides: A joint molecular dynamics/NMR study}, journal = {J. Am. Chem. Soc.}, volume = {129}, number = {5}, year = {2007}, month = {feb}, pages = {1179{\textendash}1189}, author = {Graf, Juergen and Phuong Hoang Nguyen and Stock, Gerhard and Schwalbe, Harald} } @article {2007|1477, title = {Three hydrolases and a transferase: Comparative analysis of active-site dynamics via the BioSimGrid database}, journal = {Journal of Molecular Graphics \& Modelling}, volume = {25}, number = {6}, year = {2007}, month = {mar}, pages = {896{\textendash}902}, author = {Tai, Kaihsu and Marc Baaden and Murdock, Stuart and Wu, Bing and Ng, Muan Hong and Johnston, Steven and Boardman, Richard and Fangohr, Hans and Cox, Katherine and Essex, Jonathan W. and Sansom, Mark S. P.} } @article {2006|1407, title = {{C}oexistence of two protein folding states in the crystal structure of ribosomal protein {L}20}, journal = {Embo Rep.}, volume = {7}, year = {2006}, month = {oct}, pages = {1013{\textendash}1018}, author = {Y Timsit and Allemand, F. and Chiaruttini, C. and Springer, M.} } @article {2006|1860, title = {Conformational equilibrium in alanine-rich peptides probed by reversible stretching simulations}, journal = {J. Phys. Chem. B}, volume = {110}, number = {33}, year = {2006}, pages = {16718{\textendash}16723}, doi = {10.1021/jp0601116}, author = {J{\'e}r{\^o}me H{\'e}nin and Schulten, K. and Christophe Chipot} } @article {2006|1935, title = {HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription.}, journal = {Mol. Cell}, volume = {22}, number = {5}, year = {2006}, month = {jun}, pages = {669{\textendash}679}, publisher = {Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Building 41, B602, Bethesda, Maryland 20892, USA.}, abstract = {Although histone deacetylases (HDACs) are generally viewed as corepressors, we show that HDAC1 serves as a coactivator for the glucocorticoid receptor (GR). Furthermore, a subfraction of cellular HDAC1 is acetylated after association with the GR, and this acetylation event correlates with a decrease in promoter activity. HDAC1 in repressed chromatin is highly acetylated, while the deacetylase found on transcriptionally active chromatin manifests a low level of acetylation. Acetylation of purified HDAC1 inactivates its deacetylase activity, and mutation of the critical acetylation sites abrogates HDAC1 function in vivo. We propose that hormone activation of the receptor leads to progressive acetylation of HDAC1 in vivo, which in turn inhibits the deacetylase activity of the enzyme and prevents a deacetylation event that is required for promoter activation. These findings indicate that HDAC1 is required for the induction of some genes by the GR, and this activator function is dynamically modulated by acetylation.}, keywords = {Acetylation, Amino Acid Sequence, Animals, Binding Sites, Cell Cycle Proteins, Chromatin, Down-Regulation, genetics/metabolism, Hela Cells, Histone Acetyltransferases, Histone Deacetylases, Humans, immunology/metabolism, metabolism}, doi = {10.1016/j.molcel.2006.04.019}, author = {Yi Qiu and Yingming Zhao and Matthias Becker and Sam John and Bhavin S Parekh and Suming Huang and Anindya Hendarwanto and Elisabeth D Martinez and Yue Chen and Hanxin Lu and Nicholas L Adkins and Diana A Stavreva and Malgorzata Wiench and Philippe T Geor} } @article {2006|1466, title = {Improved Wang-Landau sampling through the use of smoothed potential-energy surfaces}, journal = {J. Chem. Phys.}, volume = {124}, number = {15}, year = {2006}, month = {apr}, author = {Phuong Hoang Nguyen and Mittag, E and Torda, AE and Stock, G} } @article {2006|1619, title = {Investigating the local flexibility of functional residues in hemoproteins}, journal = {Biophys. J.}, volume = {90}, number = {8}, year = {2006}, pages = {2706{\textendash}2717}, doi = {10.1529/biophysj.105.074997}, author = {S Sacquin-Mora and Richard Lavery} } @article {2006|1441, title = {Molecular modeling and simulation of water near model micelles: diffusion, rotational relaxation and structure at the hydration interface}, journal = {J. Phys. Chem. B}, volume = {110}, number = {23}, year = {2006}, pages = {11504{\textendash}10}, author = {Sterpone, Fabio and Marchetti, Gino and Pierleoni, Carlo and Marchi, Massimo} } @article {2006|1396, title = {Nonequilibrium molecular dynamics simulation of a photoswitchable peptide}, journal = {Chem. Phys.}, volume = {323}, number = {1}, year = {2006}, month = {mar}, pages = {36{\textendash}44}, author = {Phuong Hoang Nguyen and Stock, G} } @article {2006|1389, title = {Photoinduced conformational dynamics of a photoswitchable peptide: A nonequilibrium molecular dynamics simulation study}, journal = {Biophys. J.}, volume = {91}, number = {4}, year = {2006}, month = {aug}, pages = {1224{\textendash}1234}, author = {Phuong Hoang Nguyen and Gorbunov, Roman D. and Stock, Gerhard} } @article {2006|1842, title = {Structural changes of region 1-16 of the Alzheimer disease amyloid beta-peptide upon zinc binding and in vitro aging}, journal = {J. Biol. Chem.}, volume = {281}, number = {4}, year = {2006}, pages = {2151{\textendash}2161}, author = {Severine Zirah and Sergey A. Kozin and Alexey K Mazur and Alain Blond and Michel Cheminant and Isabelle Segalas-Milazzo and Pascale Debey and Sylvie Rebuffat} } @article {2006|1827, title = {Structure and dynamics of hydrogen bonds in the interface of a C12E6 spherical micelle in water solution: a MD study at various temperatures}, journal = {J. Phys. Chem. B}, volume = {110}, number = {37}, year = {2006}, pages = {18254{\textendash}61}, author = {Sterpone, Fabio and Pierleoni, Carlo and Briganti, Giuseppe and Marchi, Massimo} } @article {2005|1540, title = {Energy landscape of a small peptide revealed by dihedral angle principal component analysis}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {58}, number = {1}, year = {2005}, month = {jan}, pages = {45{\textendash}52}, author = {Mu, YG and Phuong Hoang Nguyen and Stock, G} } @article {2005|1538, title = {Free energy landscape and folding mechanism of a beta-hairpin in explicit water: A replica exchange molecular dynamics study}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {61}, number = {4}, year = {2005}, month = {dec}, pages = {795{\textendash}808}, author = {Phuong Hoang Nguyen and Stock, G and Mittag, E and Hu, CK and Li, MS} } @article {2005|1400, title = {Hydration and thermodynamic equilibrium of non-ionic surfactant in solution}, journal = {Coll Surf A}, volume = {261}, year = {2005}, pages = {93{\textendash}99}, author = {Briganti, Giuseppe and D{\textquoteright}arrigo, Giovanni and Maccarini, Marco and Pierleoni, Carlo and Sterpone, Fabio} } @article {2005|1476, title = {Membrane protein structure quality in molecular dynamics simulation}, journal = {Journal of Molecular Graphics \& Modelling}, volume = {24}, number = {2}, year = {2005}, note = {International Meeting of the Molecular-Graphics-and-Modelling-Society, Manchester, ENGLAND, 2004}, month = {oct}, pages = {157{\textendash}165}, author = {Law, RJ and Capener, C and Marc Baaden and Bond, PJ and Campbell, J and Patargias, G and Arinaminpathy, Y and Sansom, MSP} } @article {2005|1508, title = {Modular RNA architecture revealed by computational analysis of existing pseudoknots and ribosomal RNAs}, journal = {Nuc. Acids Res.}, volume = {33}, year = {2005}, pages = {1384{\textendash}1398}, author = {S. Pasquali and H.H. Gan and T. Schlick} } @article {2005|1539, title = {Structure and energy landscape of a photoswitchable peptide: A replica exchange molecular dynamics study}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {60}, number = {3}, year = {2005}, month = {aug}, pages = {485{\textendash}494}, author = {Phuong Hoang Nguyen and Mu, YG and Stock, G} } @article {2004|1537, title = {Conformational sampling and dynamics of membrane proteins from 10-nanosecond computer simulations}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {57}, number = {4}, year = {2004}, month = {dec}, pages = {783{\textendash}791}, author = {Faraldo-Gomez, JD and Forrest, LR and Marc Baaden and Bond, PJ and Domene, C and Patargias, G and Cuthbertson, J and Sansom, MSP} } @inbook {2004|1730, title = {Conformational transitions in proteins and membranes}, booktitle = {Novel Approaches to the Structure and Dynamics of Liquids: Experiments, Theories and Simulations}, year = {2004}, pages = {485{\textendash}502}, publisher = {Springer Netherlands}, organization = {Springer Netherlands}, author = {Smith, Jeremy C and Cournia, Zoe and Antoine Taly and Tournier, Alexander L and Mihailescu, Dan and Ullmann, G Matthias} } @article {2004|1647, title = {Critical role of the C-terminal segment in the maturation and export to the cell surface of the homopentameric $\alpha$7{\textendash}5HT3A receptor}, journal = {Eur. J. Neurosci.}, volume = {20}, number = {8}, year = {2004}, pages = {2022{\textendash}2030}, publisher = {Wiley Online Library}, author = {Pons, S and Sallette, J and Bourgeois, JP and Antoine Taly and Jean-Pierre Changeux and Devillers-Thi{\'e}ry, A} } @article {2004|1807, title = {The C-terminal domain of Escherichia coli Hfq increases the stability of the hexamer}, journal = {Eur. J. Biochem.}, volume = {271}, number = {7}, year = {2004}, month = {apr}, pages = {1258{\textendash}1265}, doi = {10.1111/j.1432-1033.2004.04026.x}, author = {Arluison, V and Folichon, M and Marco, S and Philippe Derreumaux and Pellegrini, O and Seguin, J and Hajnsdorf, E and Regnier, P} } @article {2004|1939, title = {Early steps of amyloid-petide oligomerisation explored by simulations}, journal = {Neurobiol. Aging}, volume = {25}, number = {Suppl. 2}, year = {2004}, month = {jul}, pages = {S143}, doi = {10.1016/S0197-4580(04)80481-0}, author = {Philippe Derreumaux and Wei, GH and Santini, S and Mousseau, NN} } @article {2004|1791, title = {Helix H1 of the prion protein is rather stable against environmental perturbations: molecular dynamics of mutation and deletion variants of PrP(90-231)}, journal = {Cell. Mol. Life Sci.}, volume = {61}, number = {7-8}, year = {2004}, month = {apr}, pages = {951{\textendash}960}, doi = {10.1007/s00018-003-3455-3}, author = {Santini, S and Philippe Derreumaux} } @article {2004|1825, title = {Identification of the subunit-subunit interface of Xenopus Rad51.1 protein: Similarity to RecA}, journal = {J. Mol. Biol.}, volume = {335}, number = {4}, year = {2004}, month = {jan}, pages = {895{\textendash}904}, abstract = {

Rad51, like its prokaryotic homolog RecA, forms a helical filament for homologous DNA recombination and recombinational DNA repair. Comparison of the three-dimensional structures of human Rad51 and Escherichia coli RecA indicated that the tyrosine residue at position 191 in human Rad51 lies at the centre of a putative subunit-subunit contact interface. We inserted a tryptophan residue as a fluorescent probe at the corresponding position in Xenopus Rad51.1 and found that its fluorescence depended upon the protein concentration, indicating that the residue is truly in the subunit-subunit interface. We also found that 3 M urea, which promoted the dissociation of Rad51 filament without complete unfolding of the protein, exposed the tryptophan residue to solvent. The fluorescence was not modified by binding to DNA and only slightly modified by ATP, indicating that the same site is used for formation of the active ATP-Rad51-DNA filament. The slight changes in fluorescence caused by ATP and ADP suggest that the subunit-subunit contact is altered, leading to the elongation of the filament by these nucleotides, as with the RecA filament. Thus, Rad51 forms filaments by subunit-subunit contact much like RecA does.

}, author = {Selmane, T and Camadro, JM and Conilleau, S and Fleury, F and Tran, V and Chantal Pr{\'e}vost and Takahashi, M} } @article {2004|1930, title = {In silico assembly of Alzheimer{\textquoteright}s A beta(16-22) peptide into beta-sheets}, journal = {J. Am. Chem. Soc.}, volume = {126}, number = {37}, year = {2004}, month = {sep}, pages = {11509{\textendash}11516}, doi = {10.1021/ja047286i}, author = {Santini, S and Mousseau, N and Philippe Derreumaux} } @article {2004|1801, title = {Molecular cloning of a mollusk glucanase}, journal = {Comp. Biochem. Physiol.}, volume = {137}, number = {2}, year = {2004}, pages = {169{\textendash}178}, author = {Valeri B. Kozhemyako and Denis V. Rebrikov and Sergey A. Lukyanov and Ekaterina A. Bogdanova and Antoine Marin and Alexey K Mazur and Svetlana N. Kovalchuk and Elena V. Agafonova and Victoria V. Sova and Ludmila A. Elyakova and Valeri A. Rasskazov} } @article {2004|1493, title = {Molecular dynamics study of temperature dehydration of a C12E6 spherical micelle}, journal = {Langmuir}, volume = {20}, number = {11}, year = {2004}, pages = {4311{\textendash}4}, author = {Sterpone, Fabio and Pierleoni, Carlo and Briganti, Giuseppe and Marchit, Massimo} } @article {2004|1826, title = {Molecular Modeling and Simulations of AOT{\^a}{\textasciicircum}{\textquoteright}Water Reverse Micelles in Isooctane:{\^a}{\texteuro}{\textperthousand} Structural and Dynamic Properties}, journal = {J. Phys. Chem. B}, volume = {108}, number = {50}, year = {2004}, pages = {19458{\textendash}19466}, author = {Abel, St{\'e}phane and Sterpone, Fabio and Bandyopadhyay, Sanjoy and Marchi, Massimo} } @article {2004, title = {OmpT: Molecular dynamics simulations of an outer membrane enzyme}, journal = {Biophys. J.}, volume = {87}, number = {5}, year = {2004}, month = {nov}, pages = {2942{\textendash}2953}, author = {Marc Baaden and Sansom, MSP} } @article {2004|1994, title = {Pathway complexity of Alzheimer{\textquoteright}s beta-amyloid A beta(16-22) peptide assembly}, journal = {Structure}, volume = {12}, number = {7}, year = {2004}, month = {jul}, pages = {1245{\textendash}1255}, doi = {10.1016/j.str.2004.04.018}, author = {Santini, S and Wei, GH and Mousseau, N and Philippe Derreumaux} } @article {2004|1718, title = {Temperature dehydration of C12E6 micelle}, journal = {Langmuir}, volume = {20}, year = {2004}, pages = {4311{\textendash}4314}, author = {Fabio Sterpone and C. Pierleoni and G. Briganti and M. Marchi} } @article {2004|1878, title = {Torsion-induced phase transitions in fluids confined between chemically decorated substrates}, journal = {J. Chem. Phys.}, volume = {121}, number = {18}, year = {2004}, month = {nov}, pages = {9077{\textendash}9086}, doi = {10.1063/1.1804154}, author = {S Sacquin-Mora and Fuchs, AH and Schoen, M} } @article {2003|1428, title = {Exploring the folding pathways of proteins through energy landscape sampling: Application to Alzheimer{\textquoteright}s beta-amyloid peptide}, journal = {Internet Electron. J. Mol. Des.}, volume = {2}, year = {2003}, pages = {564{\textendash}577}, author = {S. Santini and G. Wei and N. Mousseau and Philippe Derreumaux} } @article {2003|1507, title = {Exploring The Repertoire of RNA Secondary Motifs Using Graph Theory with Implications for RNA Design}, journal = {Nuc. Acids Res.}, volume = {31}, year = {2003}, pages = {2926{\textendash}2943}, author = {H. H. Gan and S. Pasquali and and T. Schlick} } @article {2003, title = {Extending the structure of an ABC transporter to atomic resolution: Modeling and simulation studies of MsbA}, journal = {Biochemistry}, volume = {42}, number = {13}, year = {2003}, month = {apr}, pages = {3666{\textendash}3673}, author = {Campbell, JD and Biggin, PC and Marc Baaden and Sansom, MSP} } @article {2003|1706, title = {Fluid phase transitions at chemically heterogeneous, nonplanar solid substrates: Surface versus confinement effects}, journal = {J. Chem. Phys.}, volume = {118}, number = {3}, year = {2003}, month = {jan}, pages = {1453{\textendash}1465}, doi = {10.1063/1.1529683}, author = {S Sacquin-Mora and Schoen, M. and Fuchs, A. H.} } @mastersthesis {2003|1561, title = {Fluide nanoconfines dans des systemes de basse symetrie : Simulations et Theorie}, year = {2003}, school = {Universit{\'e} Paris XI, Orsay}, type = {phd}, author = {S Sacquin-Mora} } @article {2003|1990, title = {Impact of the tail and mutations G131V and M129V on prion protein flexibility}, journal = {Proteins-structure Function and Genetics}, volume = {51}, number = {2}, year = {2003}, month = {may}, pages = {258{\textendash}265}, doi = {10.1002/prot.10348}, author = {Santini, S and Claude, JB and Audic, S and Philippe Derreumaux} } @article {2003|1694, title = {Linear response and electron transfer in complex biomolecules systems and Reaction Center Protein}, journal = {J. Phys. Chem. B}, volume = {107}, year = {2003}, pages = {11208{\textendash}11215}, author = {Fabio Sterpone and M. Ceccarelli and M. Marchi} } @article {2003|1465, title = {Local structure in nematic and isotropic liquid crystals}, journal = {J. Chem. Phys.}, volume = {119}, number = {2}, year = {2003}, month = {jul}, pages = {1214{\textendash}1222}, author = {Phuong, NH and Schmid, F} } @article {2003|1475, title = {A molecular dynamics investigation of mono and dimeric states of the outer membrane enzyme OMPLA}, journal = {J. Mol. Biol.}, volume = {331}, number = {1}, year = {2003}, month = {aug}, pages = {177{\textendash}189}, author = {Marc Baaden and Meier, C and Sansom, MSP} } @article {2003|1957, title = {Nanoscopic liquid bridges exposed to a torsional strain}, journal = {Physical Review E}, volume = {68}, number = {6, Part 2}, year = {2003}, month = {dec}, pages = {066103}, doi = {10.1103/PhysRevE.68.066103}, author = {S Sacquin-Mora and Fuchs, AH and Schoen, M} } @article {2003|1464, title = {Nonequilibrium molecular-dynamics study of the vibrational energy relaxation of peptides in water}, journal = {J. Chem. Phys.}, volume = {119}, number = {21}, year = {2003}, month = {dec}, pages = {11350{\textendash}11358}, author = {Phuong Hoang Nguyen and Stock, G} } @article {2003|1621, title = {The position of Q B in the photosynthetic reaction center depends on pH: A theoretical analysis of the proton uptake upon Q B reduction}, journal = {Biophys. J.}, volume = {84}, number = {3}, year = {2003}, pages = {2090{\textendash}2098}, publisher = {Cell Press}, author = {Antoine Taly and Sebban, Pierre and Smith, Jeremy C and Ullmann, G Matthias} } @article {2003|1548, title = {Theoretical studies on lanthanide cation extraction by picolinamides: Ligand-cation interactions and interfacial behavior}, journal = {Solvent Extr. Ion Exch.}, volume = {21}, number = {2}, year = {2003}, pages = {199{\textendash}220}, author = {Marc Baaden and Berny, F and Madic, C and Schurhammer, R and Wipff, G} } @article {2002, title = {Analysis of Protein Sequence/Structure Similarity Relationships}, journal = {Biophys. J.}, volume = {83}, year = {2002}, pages = {2781{\textendash}2791}, author = {H. H. Gan and R. A. Perow and S. Roy and J. Ko, M. Wu, J. Huang and S. Yan and A. Nicoletta and J. Vafai, D. Sun and L. Wang and J. E. Noah and S. Pasquali and T. Schlick} } @conference {2002|1622, title = {Cd2+ binding effect on bacterial reaction center mutants: The proton penetration involves interdependent pathways}, booktitle = {BIOPHYSICAL JOURNAL}, volume = {82}, number = {1}, year = {2002}, pages = {518A-518A}, publisher = {BIOPHYSICAL SOCIETY 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA}, organization = {BIOPHYSICAL SOCIETY 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA}, author = {Gerencser, L and Antoine Taly and Baciou, L and Maroti, P and Sebban, P} } @article {2002|1402, title = {The direct correlation function in nematic liquid crystals from computer simulation}, journal = {Comput. Phys. Commun.}, volume = {147}, number = {1-2}, year = {2002}, note = {Europhysics Conference on Computational Physics (CCP 2001), AACHEN, GERMANY, SEP 05-08, 2001}, month = {aug}, pages = {350{\textendash}353}, author = {Phuong, NH and Germano, G and Schmid, F} } @article {2002|2002, title = {{E}ffect of binding of {C}d2+ on bacterial reaction center mutants: proton-transfer uses interdependent pathways}, journal = {Biochemistry}, volume = {41}, number = {29}, year = {2002}, month = {jul}, pages = {9132{\textendash}9138}, publisher = {ACS Publications}, author = {Gerencser, L. and Antoine Taly and Baciou, L. and Maroti, P. and Sebban, P.} } @article {2002|1726, title = {Fluids confined by nanopatterned substrates of low symmetry}, journal = {Mol. Phys.}, volume = {100}, number = {18}, year = {2002}, month = {sep}, pages = {2971{\textendash}2982}, doi = {10.1080/00268970210121632}, author = {S Sacquin-Mora and Schoen, M. and Fuchs, A. H.} } @article {2002|1483, title = {Molecular dynamics study of the uranyl extraction by tri-n-butylphosphate (TBP): Demixing of water/{{\textquoteright}{\textquoteright}}oil{{\textquoteright}{\textquoteright}}/TBP solutions with a comparison of supercritical CO2 and chloroform}, journal = {J. Phys. Chem. B}, volume = {106}, number = {2}, year = {2002}, month = {jan}, pages = {434{\textendash}441}, author = {Marc Baaden and Schurhammer, R and Wipff, G} } @conference {2002|1502, title = {Spatial order in liquid crystals: Computer simulations of systems of ellipsoids}, booktitle = {MORPHOLOGY OF CONDENSED MATTER: PHYSICS AND GEOMETRY OF SPATIALLY COMPLEX SYSTEMS}, series = {Lecture Notes in Physics}, volume = {600}, year = {2002}, note = {2nd International Wuppertal Workshop on Statistical Physics and Spatial Statistics, UNIV WUPPERTAL, WUPPERTAL, GERMANY, MAR 05-09, 2001}, pages = {172{\textendash}186}, author = {Schmid, F and Phuong, NH}, editor = {Mecke, K and Stoyan, D} } @article {2002|1650, title = {{T}he {D}{M}{P}{C} lipid phase transition influences differently the first and the second electron transfer reactions in bacterial reaction centers}, journal = {Febs Lett.}, volume = {532}, number = {1-2}, year = {2002}, month = {dec}, pages = {91{\textendash}96}, author = {Antoine Taly and Baciou, L. and Sebban, P.} } @article {2002|1817, title = {Water rotational relaxation and diffusion in hydrated lysozyme}, journal = {J. Am. Chem. Soc.}, volume = {124}, number = {23}, year = {2002}, month = {jun}, pages = {6787{\textendash}91}, abstract = {This paper is concerned with the dynamics of water around a small globular protein. Dipolar second-rank relaxation time and diffusion properties of surface water were computed by extensive molecular dynamics simulations of lysozyme in water which lasted a total of 28 ns. Our results indicate that the rotational relaxation of water in the vicinity of lysozyme is 3-7 times slower than that in the bulk depending on how the hydration shell is defined in the calculation. We have also verified that the dynamics of water translational diffusion in the vicinity of lysozyme have retardations similar to rotational relaxation. This is a common assumption in nuclear magnetic relaxation dispersion (NMRD) studies to derive residence times. In contrast to bulk water dynamics, surface water is in a dispersive diffusion regime or subdiffusion. Very good agreement of dipolar second-rank relaxation time with NMRD estimates is obtained by using appropriate dimensions of the hydration shell. Although our computed second-rank dipolar retardations are independent of the water model, SPC/E describes more realistically the time scale of the water dynamics around lysozyme than does TIP3P.}, author = {Marchi, Massimo and Sterpone, Fabio and Ceccarelli, Matteo} } @article {2001|1823, title = {Dynamics of hydration in hen egg white lysozyme}, journal = {J. Mol. Biol.}, volume = {311}, number = {2}, year = {2001}, month = {aug}, pages = {409{\textendash}19}, abstract = {We investigate the hydration dynamics of a small globular protein, hen egg-white lysozyme. Extensive simulations (two trajectories of 9 ns each) were carried out to identify the time-scales and mechanism of water attachment to this protein. The location of the surface and integral water molecules in lysozyme was also investigated. Three peculiar temporal scales of the hydration dynamics can be discerned: two among these, with sub-nanosecond mean residence time, tau(w), are characteristic of surface hydration water; the slower time-scale (tau(w) approximately 2/3 ns) is associated with buried water molecules in hydrophilic pores and in superficial clefts. The computed tau(w) values in the two independent runs fall in a similar range and are consistent with each other, thus adding extra weight to our result. The tau(w) of surface water obtained from the two independent trajectories is 20 and 24 ps. In both simulations only three water molecules are bound to lysozyme for the entire length of the trajectories, in agreement with nuclear magnetic relaxation dispersion estimates. Locations other than those identified in the protein crystal are found to be possible for these long-residing water molecules. The dynamics of the hydration water molecules observed in our simulations implies that each water molecule visits a multitude of residues during the lifetime of its bound with the protein. The number of residues seen by a single water molecule increases with the time-scale of its residence time and, on average, is equal to one only for the water molecules with shorter residence time. Thus, tau(w) values obtained from inelastic neutron scattering and based on jump-diffusion models are likely not to account for the contribution of water molecules with longer residence time.}, doi = {10.1006/jmbi.2001.4860}, author = {Sterpone, F and Ceccarelli, M and Marchi, M} } @article {2001|1463, title = {Elastic constants from direct correlation functions in nematic liquid crystals: A computer simulation study}, journal = {J. Chem. Phys.}, volume = {115}, number = {15}, year = {2001}, month = {oct}, pages = {7227{\textendash}7234}, author = {Phuong, NH and Germano, G and Schmid, F} } @article {2001|1802, title = {Internal coordinate phase space analysis of macromolecular systems}, journal = {Comput. Theor. Polym. Sci.}, volume = {11}, number = {1}, year = {2001}, pages = {35{\textendash}47}, author = {Alexey K Mazur and Bobby G. Sumpter and Donald W. Noid} } @article {2001|1933, title = {Molecular Dynamics Study of Spherical Aggregates of Chain Molecules at Different Degrees of Hydrophilicity in Water Solution}, journal = {Langmuir}, volume = {17}, number = {16}, year = {2001}, pages = {5103{\textendash}5110}, author = {Sterpone, Fabio and Briganti, Giuseppe and Pierleoni, Carlo} } @article {2000, title = {Calix{[}4]arenes as selective extracting agents. An NMR dynamic and conformational investigation of the lanthanide(III) and thorium(IV) complexes}, journal = {Inorg. Chem.}, volume = {39}, number = {10}, year = {2000}, month = {may}, pages = {2033{\textendash}2041}, author = {Lambert, B and Jacques, V and Shivanyuk, A and Matthews, SE and Tunayar, A and Marc Baaden and Wipff, G and Bohmer, V and Desreux, JF} } @article {2000|1501, title = {Dependence of NMR isotropic shift averages and nuclear shielding tensors on the internal rotation of the functional group X about the C-X bond in seven simple vinylic derivatives H2C=CH-X}, journal = {Mol. Phys.}, volume = {98}, number = {6}, year = {2000}, month = {mar}, pages = {329{\textendash}342}, author = {Marc Baaden and Granger, P and Strich, A} } @article {2000|1460, title = {Interaction of trivalent lanthanide cations with phosphoryl derivatives, amide, anisole, pyridine and triazine ligands: a quantum mechanics study}, journal = {J. Alloys Compd.}, volume = {303}, year = {2000}, note = {22nd Rare Earth Research Conference, ARGONNE, ILLINOIS, JUL 11-15, 1999}, month = {may}, pages = {104{\textendash}111}, author = {Marc Baaden and Berny, F and Boehme, C and Muzet, N and Schurhammer, R and Wipff, G} } @conference {2000|1532, title = {Separation of radioactive cations by liquid-liquid extraction: computer simulations of water / oil solutions of salts and ionophores}, booktitle = {Proceedings of the Euradwaste 1999 conference}, year = {2000}, pages = {390{\textendash}393}, address = {EC, Luxembourg}, author = {Marc Baaden and F. Berny and N. Muzet and R. Schurhammer and G. Wipff}, editor = {C. Davies} } @article {1999, title = {{L}eft-handed {D}{N}{A} crossovers. {I}mplications for {D}{N}{A}-{D}{N}{A} recognition and structural alterations}, journal = {J. Biomol. Struct. Dyn.}, volume = {16}, year = {1999}, month = {feb}, pages = {775{\textendash}785}, author = {Y Timsit and Shatzky-Schwartz, M. and Shakked, Z.} } @article {1998|1454, title = {{D}{N}{A} crossovers and type {I}{I} {D}{N}{A} topoisomerases: {A} thermodynamical study}, journal = {J. Mol. Biol.}, volume = {284}, year = {1998}, month = {dec}, pages = {1279{\textendash}1287}, author = {Sikorav, J.L. and Duplantier, B. and Jannink, G. and Y Timsit} } @article {1998|1624, title = {The loop opening/closing motion of the enzyme triosephosphate isomerase}, journal = {Biophys. J.}, volume = {74}, number = {1}, year = {1998}, month = {jan}, pages = {72{\textendash}81}, author = {Philippe Derreumaux and Schlick, T.} } @article {1998|1453, title = {{S}ymmetry and chirality in topoisomerase {I}{I}-{D}{N}{A} crossover recognition}, journal = {J. Mol. Biol.}, volume = {284}, year = {1998}, month = {dec}, pages = {1289{\textendash}1299}, author = {Y Timsit and Duplantier, B. and Jannink, G. and Sikorav, J.L.} } @article {1996|1666, title = {Finding and visualizing nucleic acid base stacking}, journal = {J Mol Graph}, volume = {14}, number = {1}, year = {1996}, month = {feb}, pages = {6{\textendash}11}, author = {Gabb, H A and Sanghani, S R and Charles H. Robert and Chantal Pr{\'e}vost} } @article {1995|1988, title = {LONG TIMESTEP DYNAMICS OF PEPTIDES BY THE DYNAMICS DRIVER APPROACH}, journal = {Proteins-structure Function and Genetics}, volume = {21}, number = {4}, year = {1995}, month = {apr}, pages = {282{\textendash}302}, doi = {10.1002/prot.340210403}, author = {Philippe Derreumaux and SCHLICK, T} } @article {1995, title = {Radiation-induced damages in single- and double-stranded DNA}, journal = {Int. J. Radiat. Biol.}, volume = {67}, year = {1995}, month = {feb}, pages = {169{\textendash}76}, abstract = {

In the present study, we searched for possible effects of DNA strandedness (single and double), on two types of damages, frank strand breaks (FSB, observed at neutral pH) and alkali labile sites (ALS, leading to breaks at alkaline pH) induced by irradiation with gamma-rays (60Co) or fast neutrons (p34,Be). Sequencing gel electrophoresis allowed us to follow the occurrence of these damages at each nucleotide site in single (ss-ss), double (ds-ds), and half single-half double (ss-ds and ds-ss) stranded oligonucleotides. Globally, in DNA with random sequences of bases, no differences in FSB and ALS yield between the single and the double-stranded conformations were observed. One observes, however, an increased alkaline lability at some guanine sites belonging to single-stranded region of ss-ds or ds-ss. Nevertheless, strandedness influences the radiosensitivity of some particular sequences, i.e. the 5\&$\#$39;-AATT sequences. This region is less radiosensitive than the rest of DNA in the double helical, but not in the single-stranded conformation. The results are discussed in terms of DNA conformation.

}, author = {Isabelle, V and Chantal Pr{\'e}vost and Spotheim-Maurizot, M and Sabattier, R and Charlier, M} } @article {1994|1993, title = {FORCE-FIELD AND VIBRATIONAL-SPECTRA OF OLIGOSACCHARIDES WITH DIFFERENT GLYCOSIDIC LINKAGES .2. MALTOSE MONOHYDRATE, CELLOBIOSE AND GENTIOBIOSE}, journal = {Spectrochimica Acta Part A-molecular and Biomolecular Spectroscopy}, volume = {50}, number = {1}, year = {1994}, month = {jan}, pages = {105{\textendash}118}, doi = {10.1016/0584-8539(94)80118-5}, author = {Dauchez, M and LAGANT, P and Philippe Derreumaux and VERGOTEN, G and SEKKAL, M and SOMBRET, B} } @article {1994|1992, title = {FORCE-FIELD AND VIBRATIONAL-SPECTRA OF OLIGOSACCHARIDES WITH DIFFERENT GLYCOSIDIC LINKAGES .1. TREHALOSE DIHYDRATE, SOPHOROSE MONOHYDRATE AND LAMINARIBIOSE}, journal = {Spectrochimica Acta Part A-molecular and Biomolecular Spectroscopy}, volume = {50}, number = {1}, year = {1994}, month = {jan}, pages = {87{\textendash}104}, doi = {10.1016/0584-8539(94)80117-7}, author = {Dauchez, M and Philippe Derreumaux and LAGANT, P and VERGOTEN, G and SEKKAL, M and LEGRAND, P} } @article {1994|1968, title = {Three-dimensional structure of extended chromatin fibers as revealed by tapping-mode scanning force microscopy}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {91}, number = {24}, year = {1994}, month = {nov}, pages = {11621{\textendash}11625}, abstract = {Unfixed chicken erythrocyte chromatin fibers in very low salt have been imaged with a scanning force microscope operating in the tapping mode in air at ambient humidity. These images reveal a three-dimensional organization of the fibers. The planar "zig-zag" conformation is rare, and extended "beads-on-a-string" fibers are seen only in chromatin depleted of histones H1 and H5. Glutaraldehyde fixation reveals very similar structures. Fibers fixed in 10 mM salt appear somewhat more compacted. These results, when compared with modeling studies, suggest that chromatin fibers may exist as irregular three-dimensional arrays of nucleosomes even at low ionic strength.}, keywords = {Animals, Atomic Force, Biological, Chickens, Chromatin, Fixatives, Histones, Microscopy, Models, Non-P.H.S., Non-U.S. Gov{\textquoteright}t, Osmolar Concentration, P.H.S., Research Support, Sodium Chloride, U.S. Gov{\textquoteright}t}, author = {S. H. Leuba and G. Yang and C. Robert and B. Samori and K. van Holde and J. Zlatanova and C. Bustamante} } @article {1994|1897, title = {A TRUNCATED NEWTON MINIMIZER ADAPTED FOR CHARMM AND BIOMOLECULAR APPLICATIONS}, journal = {J. Comput. Chem.}, volume = {15}, number = {5}, year = {1994}, month = {may}, pages = {532{\textendash}552}, doi = {10.1002/jcc.540150506}, author = {Philippe Derreumaux and ZHANG, GH and SCHLICK, T and BROOKS, B} } @article {1992|1596, title = {Kinetics of pore-mediated release of marker molecules from liposomes or cells}, journal = {Biophys. Chem.}, volume = {42}, number = {3}, year = {1992}, month = {apr}, pages = {291{\textendash}296}, author = {Schwarz, G and Charles H. Robert} } @article {1991|1593, title = {A combined study of aggregation, membrane affinity and pore activity of natural and modified melittin}, journal = {Biochim. Biophys. Acta}, volume = {1069}, number = {1}, year = {1991}, month = {oct}, pages = {77{\textendash}86}, author = {Stankowski, S and Pawlak, M and Kaisheva, E and Charles H. Robert and Schwarz, G} } @conference {1991|1580, title = {Methodological considerations on molecular dynamics simulations of DNA oligonucleotides}, booktitle = {AIP Conference Proceedings}, year = {1991}, month = {oct}, publisher = {AIP}, organization = {AIP}, abstract = {

Methodological aspects of solvent effects, simulation protocol, analysis and visualization of results, accuracy, and sensitivity of results to force field parametrization are discussed for molecular dynamics simulation on oligonucleotides. Recent results comparing AMBER, CHARMM and GROMOS force fields are included. The calculation of build\‚{\"A}{\^e}up curves for the nuclear Overhauser effect from simulations is also described.

}, doi = {10.1063/1.41314}, author = {Beveridge, DL and Swaminathan, S and Ravishanker, G and Withka, J and Srinivasan, J and Chantal Pr{\'e}vost and Louise-May, S and DiCapua, FM and Bolton, PH} } @article {1990, title = {Pore formation kinetics in membranes, determined from the release of marker molecules out of liposomes or cells}, journal = {Biophys. J.}, volume = {58}, year = {1990}, pages = {577{\textendash}583}, author = {Schwarz, Gerhard and Charles H. Robert} } @article {1986|1595, title = {A study of interaction of an O-specific polysaccharide from Pseudomonas fluorescense with antibodies}, journal = {Bioorg. Chem.}, volume = {12}, year = {1986}, pages = {265{\textendash}272}, author = {T. F. Solovjeva and G. A. Naberezhnykh and Alexey K Mazur and V. A. Khomenko and Yu. S. Ovodov} }