@article {2025, title = {Impact of multiple phosphorylations on the tau-R2/tubulin interface}, journal = {Biochemistry}, year = {2025}, 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.

}, author = {Marien, Jules and Pr{\'e}vost, Chantal and S Sacquin-Mora} } @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 {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|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 {2023|2164, title = {Molecular determinants of inhibition of UCP1-mediated respiratory uncoupling.}, journal = {Nat Commun}, volume = {14}, year = {2023}, month = {2023 May 05}, pages = {2594}, abstract = {

Brown adipose tissue expresses uncoupling protein 1 (UCP1), which dissipates energy as heat, making it a target for treating metabolic disorders. Here, we investigate how purine nucleotides inhibit respiration uncoupling by UCP1. Our molecular simulations predict that GDP and GTP bind UCP1 in the common substrate binding site in an upright orientation, where the base moiety interacts with conserved residues R92 and E191. We identify a triplet of uncharged residues, F88/I187/W281, forming hydrophobic contacts with nucleotides. In yeast spheroplast respiration assays, both I187A and W281A mutants increase the fatty acid-induced uncoupling activity of UCP1 and partially suppress the inhibition of UCP1 activity by nucleotides. The F88A/I187A/W281A triple mutant is overactivated by fatty acids even at high concentrations of purine nucleotides. In simulations, E191 and W281 interact with purine but not pyrimidine bases. These results provide a molecular understanding of the selective inhibition of UCP1 by purine nucleotides.

}, keywords = {Adipose Tissue, Brown, Fatty Acids, Ion Channels, Membrane Proteins, Mitochondrial Proteins, Purine Nucleotides, Saccharomyces cerevisiae, Uncoupling Protein 1}, issn = {2041-1723}, doi = {10.1038/s41467-023-38219-9}, author = {Gagelin, Antoine and Largeau, Corentin and Masscheleyn, Sandrine and Piel, Mathilde S and Calder{\'o}n-Mora, Daniel and Bouillaud, Fr{\'e}d{\'e}ric and J{\'e}r{\^o}me H{\'e}nin and Miroux, Bruno} } @article {2022|2156, title = {Building Biological Relevance Into Integrative Modelling of Macromolecular Assemblies}, journal = {Frontiers in Molecular Biosciences}, volume = {9}, year = {2022}, pages = {826136}, abstract = {

Recent advances in structural biophysics and integrative modelling methods now allow us to decipher the structures of large macromolecular assemblies. Understanding the dynamics and mechanisms involved in their biological function requires rigorous integration of all available data. We have developed a complete modelling pipeline that includes analyses to extract biologically significant information by consistently combining automated and interactive human-guided steps. We illustrate this idea with two examples. First, we describe the ryanodine receptor, an ion channel that controls ion flux across the cell membrane through transitions between open and closed states. The conformational changes associated with the transitions are small compared to the considerable system size of the receptor; it is challenging to consistently track these states with the available cryo-EM structures. The second example involves homologous recombination, in which long filaments of a recombinase protein and DNA catalyse the exchange of homologous DNA strands to reliably repair DNA double-strand breaks. The nucleoprotein filament reaction intermediates in this process are short-lived and heterogeneous, making their structures particularly elusive. The pipeline we describe, which incorporates experimental and theoretical knowledge combined with state-of-the-art interactive and immersive modelling tools, can help overcome these challenges. In both examples, we point to new insights into biological processes that arise from such interdisciplinary approaches.

}, issn = {2296-889X}, doi = {10.3389/fmolb.2022.826136}, url = {https://www.frontiersin.org/article/10.3389/fmolb.2022.826136}, author = {Molza, Anne-Elisabeth and Westermaier, Yvonne and Moutte, Magali and Ducrot, Pierre and Danilowicz, Claudia and Godoy-Carter, Veronica and Prentiss, Mara and Robert, Charles H. and Marc Baaden and Pr{\'e}vost, Chantal} } @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|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 {2020|2145, title = {Binding of divalent cations to acetate: molecular simulations guided by Raman spectroscopy}, journal = {Phys. Chem. Chem. Phys.}, volume = {22}, year = {2020}, pages = {24014-24027}, chapter = {24014}, abstract = {

In spite of the biological importance of the binding of Zn2+, Ca2+, and Mg2+ to the carboxylate group, cation\–acetate binding affinities and binding modes remain actively debated. Here, we report the first use of Raman multivariate curve resolution (Raman-MCR) vibrational spectroscopy to obtain self-consistent free and bound metal acetate spectra and one-to-one binding constants, without the need to invoke any a priori assumptions regarding the shapes of the corresponding vibrational bands. The experimental results, combined with classical molecular dynamics simulations with a force field effectively accounting for electronic polarization via charge scaling and ab initio simulations, indicate that the measured binding constants pertain to direct (as opposed to water separated) ion pairing. The resulting binding constants do not scale with cation size, as the binding constant to Zn2+ is significantly larger than that to either Mg2+ or Ca2+, although Zn2+ and Mg2+ have similar radii that are about 25\% smaller than Ca2+. Remaining uncertainties in the metal acetate binding free energies are linked to fundamental ambiguities associated with identifying the range of structures pertaining to non-covalently bound species.

}, doi = {10.1039/D0CP02987D}, url = {https://pubs.rsc.org/en/content/articlelanding/2020/cp/d0cp02987d$\#$!divAbstract}, author = {Mendes de Oliveira, Denilson and Samual R. Zukowski and Vladimir Palivec and J{\'e}r{\^o}me H{\'e}nin and Hector Martinez-Seara and Dor Ben-Amotz and Pavel Jungwirth and Elise Dubou{\'e}-Dijon} } @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|2130, title = {Direct Homologous dsDNA-dsDNA Pairing: How, Where, and Why?}, journal = {J Mol Biol}, volume = {432}, year = {2020}, month = {2020 Feb 07}, pages = {737-744}, abstract = {

The ability of homologous chromosomes (or selected chromosomal loci) to pair specifically in the apparent absence of DNA breakage and recombination represents a prominent feature of eukaryotic biology. The mechanism of homology recognition at the basis of such recombination-independent pairing has remained elusive. A number of studies have supported the idea that sequence homology can be sensed between intact DNA double helices in vivo. In particular, recent analyses of the two silencing phenomena in fungi, known as \"repeat-induced point mutation\" (RIP) and \"meiotic silencing by unpaired DNA\" (MSUD), have provided genetic evidence for the existence of the direct homologous dsDNA-dsDNA pairing. Both RIP and MSUD likely rely on the same search strategy, by which dsDNA segments are matched as arrays of interspersed base-pair triplets. This process is general and very efficient, yet it proceeds normally without the RecA/Rad51/Dmc1 proteins. Further studies of RIP and MSUD may yield surprising insights into the function of DNA in the cell.

}, issn = {1089-8638}, doi = {10.1016/j.jmb.2019.11.005}, author = {Mazur, Alexey K and Nguyen, Tinh-Suong and Gladyshev, Eugene} } @article {2020|2143, title = {A practical guide to biologically relevant molecular simulations with charge scaling for electronic polarization.}, journal = {J Chem Phys}, volume = {153}, year = {2020}, month = {2020 Aug 07}, pages = {050901}, abstract = {

Molecular simulations can elucidate atomistic-level mechanisms of key biological processes, which are often hardly accessible to experiment. However, the results of the simulations can only be as trustworthy as the underlying simulation model. In many of these processes, interactions between charged moieties play a critical role. Current empirical force fields tend to overestimate such interactions, often in a dramatic way, when polyvalent ions are involved. The source of this shortcoming is the missing electronic polarization in these models. Given the importance of such biomolecular systems, there is great interest in fixing this deficiency in a computationally inexpensive way without employing explicitly polarizable force fields. Here, we review the electronic continuum correction approach, which accounts for electronic polarization in a mean-field way, focusing on its charge scaling variant. We show that by pragmatically scaling only the charged molecular groups, we qualitatively improve the charge-charge interactions without extra computational costs and benefit from decades of force field development on biomolecular force fields.

}, issn = {1089-7690}, doi = {10.1063/5.0017775}, author = {Dubou{\'e}-Dijon, E and Javanainen, M and Delcroix, P and Jungwirth, P and Martinez-Seara, H} } @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|2098, title = {Scruter les mol{\'e}cules en r{\'e}alit{\'e} virtuelle, pour quoi faire ?}, journal = {L{\textquoteright}Actualit{\'e} Chimique}, year = {2020}, pages = {23{\textendash}26}, abstract = {

Les repr{\'e}sentations des mol{\'e}cules ont pris une place importante dans la communication d\’id{\'e}es, la g{\'e}n{\'e}ration d\’hypoth{\`e}ses sur les m{\'e}canismes biologiques et l\’analyse de simulations mol{\'e}culaires. Pourtant, les dispositifs pour les observer et les manipuler restent souvent cantonn{\'e}s aux deux dimensions des {\'e}crans et {\`a} l\’interaction limit{\'e}e d\’une souris et d\’un clavier. D\’autres solutions plus performantes et {\`a} port{\'e}e de tous existent, notamment avec les derni{\`e}res {\'e}volutions de la r{\'e}alit{\'e} virtuelle pour le grand public. Des adaptations sont n{\'e}anmoins n{\'e}cessaires pour b{\'e}n{\'e}ficier pleinement des avantages li{\'e}s {\`a} l\’utilisation de la r{\'e}alit{\'e} virtuelle pour la visualisation scientifique. Cet article pr{\'e}sente quelques exemples r{\'e}alis{\'e}s avec le logiciel UnityMol. En plus des applications directes dans l\’enseignement, le changement de paradigme d\’interaction et la perception accrue de la profondeur et des formes des mol{\'e}cules biologiques facilitent d{\`e}s {\`a} pr{\'e}sent la compr{\'e}hension de ces syst{\`e}mes complexes et am{\`e}neront certainement {\`a} la d{\'e}couverte de nouveaux savoirs scientifiques.

}, issn = {0151-9093}, url = {http://www.lactualitechimique.org/Scruter-les-molecules-en-realite-virtuelle-pour-quoi-faire}, author = {Martinez, Xavier and Marc Baaden} } @article {2020|2131, title = {Tau R3-R4 Domain Dimer of the Wild Type and Phosphorylated Ser356 Sequences. I. In Solution by Atomistic Simulations.}, journal = {J Phys Chem B}, year = {2020}, month = {2020 Mar 27}, abstract = {

In Alzheimer\&$\#$39;s disease, neurofibrillary lesions correlate with cognitive deficits and consist of inclusions of tau protein with cross-β structure. A stable dimeric form of soluble tau has been evidenced in the cells, but its high-resolution structure is missing in solution. We know, however, that cryo-electron microscopy (c-EM) of full-length tau in the brain of an individual with AD displays a core of eight β-sheets with a C-shaped architecture spanning the R3-R4 repeat domain, while the rest of the protein is very flexible. To address the conformational ensemble of the dimer, we performed atomistic replica exchange molecular dynamics simulations on the tau R3-R4 domain starting from the c-EM configuration. We find that the wild type tau R3-R4 dimer explores elongated, U-shaped, V-shaped and globular forms rather than the C-shape. Phosphorylation of Ser356, pSer356, is known to block the interaction between the tau protein and the amyloid-β42 peptide. Standard molecular dynamics simulations of this phosphorylated sequence for a total of 5 microseconds compared to its wild type counterpart show a modulation of the population of β-helices and accessible topologies, and a decrease of intermediates near the fibril like conformers.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.0c00574}, author = {Philippe Derreumaux and Man, Viet Hoang and Wang, Junmei and Phuong Hoang Nguyen} } @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|2077, title = {Visualizing biomolecular electrostatics in virtual reality with UnityMol-APBS.}, journal = {Protein Sci}, volume = {29}, year = {2020}, month = {2020 Jan}, pages = {237-246}, abstract = {

Virtual reality is a powerful tool with the ability to immerse a user within a completely external environment. This immersion is particularly useful when visualizing and analyzing interactions between small organic molecules, molecular inorganic complexes, and biomolecular systems such as redox proteins and enzymes. A common tool used in the biomedical community to analyze such interactions is the Adaptive Poisson-Boltzmann Solver (APBS) software, which was developed to solve the equations of continuum electrostatics for large biomolecular assemblages. Numerous applications exist for using APBS in the biomedical community including analysis of protein ligand interactions and APBS has enjoyed widespread adoption throughout the biomedical community. Currently, typical use of the full APBS toolset is completed via the command line followed by visualization using a variety of two-dimensional external molecular visualization software. This process has inherent limitations: visualization of three-dimensional objects using a two-dimensional interface masks important information within the depth component. Herein, we have developed a single application, UnityMol-APBS, that provides a dual experience where users can utilize the full range of the APBS toolset, without the use of a command line interface, by use of a simple graphical user interface (GUI) for either a standard desktop or immersive virtual reality experience.

}, issn = {1469-896X}, doi = {10.1002/pro.3773}, author = {Laureanti, Joseph and Brandi, Juan and Offor, Elvis and Engel, David and Rallo, Robert and Ginovska, Bojana and Martinez, Xavier and Marc Baaden and Baker, Nathan A} } @article {2020|2074, title = {Visualizing protein structures - tools and trends.}, journal = {Biochem Soc Trans}, year = {2020}, month = {2020 Mar 20}, abstract = {

Molecular visualization is fundamental in the current scientific literature, textbooks and dissemination materials. It provides an essential support for presenting results, reasoning on and formulating hypotheses related to molecular structure. Tools for visual exploration of structural data have become easily accessible on a broad variety of platforms thanks to advanced software tools that render a great service to the scientific community. These tools are often developed across disciplines bridging computer science, biology and chemistry. This mini-review was written as a short and compact overview for scientists who need to visualize protein structures and want to make an informed decision which tool they should use. Here, we first describe a few \&$\#$39;Swiss Army knives\&$\#$39; geared towards protein visualization for everyday use with an existing large user base, then focus on more specialized tools for peculiar needs that are not yet as broadly known. Our selection is by no means exhaustive, but reflects a diverse snapshot of scenarios that we consider informative for the reader. We end with an account of future trends and perspectives.

}, issn = {1470-8752}, doi = {10.1042/BST20190621}, author = {Martinez, Xavier and Chavent, Matthieu and Marc Baaden} } @article {2019|2110, title = {Effects of all-atom molecular mechanics force fields on amyloid peptide assembly: the case of aβ16{\textendash}22 dimer}, journal = {Journal of chemical theory and computation}, volume = {15}, year = {2019}, pages = {1440{\textendash}1452}, author = {Man, Viet Hoang and He, Xibing and Philippe Derreumaux and Ji, Beihong and Xie, Xiang-Qun and Phuong Hoang Nguyen and Wang, Junmei} } @article {2019|2076, title = {Glutathionylation primes soluble glyceraldehyde-3-phosphate dehydrogenase for late collapse into insoluble aggregates.}, journal = {Proc Natl Acad Sci U S A}, volume = {116}, year = {2019}, month = {2019 12 17}, pages = {26057-26065}, abstract = {

Protein aggregation is a complex physiological process, primarily determined by stress-related factors revealing the hidden aggregation propensity of proteins that otherwise are fully soluble. Here we report a mechanism by which glycolytic glyceraldehyde-3-phosphate dehydrogenase of (AtGAPC1) is primed to form insoluble aggregates by the glutathionylation of its catalytic cysteine (Cys149). Following a lag phase, glutathionylated AtGAPC1 initiates a self-aggregation process resulting in the formation of branched chains of globular particles made of partially misfolded and totally inactive proteins. GSH molecules within AtGAPC1 active sites are suggested to provide the initial destabilizing signal. The following removal of glutathione by the formation of an intramolecular disulfide bond between Cys149 and Cys153 reinforces the aggregation process. Physiological reductases, thioredoxins and glutaredoxins, could not dissolve AtGAPC1 aggregates but could efficiently contrast their growth. Besides acting as a protective mechanism against overoxidation, S-glutathionylation of AtGAPC1 triggers an unexpected aggregation pathway with completely different and still unexplored physiological implications.

}, issn = {1091-6490}, doi = {10.1073/pnas.1914484116}, author = {Zaffagnini, Mirko and Marchand, Christophe H and Malferrari, Marco and Murail, Samuel and Bonacchi, Sara and Genovese, Damiano and Montalti, Marco and Venturoli, Giovanni and Falini, Giuseppe and Marc Baaden and Lemaire, St{\'e}phane D and Fermani, Simona and Trost, Paolo} } @article {2019|2108, title = {Interaction mechanism between the focused ultrasound and lipid membrane at the molecular level}, journal = {The Journal of chemical physics}, volume = {150}, year = {2019}, pages = {215101}, author = {Man, Viet Hoang and Li, Mai Suan and Wang, Junmei and Philippe Derreumaux and Phuong Hoang Nguyen} } @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|2079, title = {Molecular Graphics: Bridging Structural Biologists and Computer Scientists.}, journal = {Structure}, volume = {27}, year = {2019}, month = {2019 11 05}, pages = {1617-1623}, abstract = {

Visualization of molecular structures is one of the most common tasks carried out by structural biologists, typically using software, such as Chimera, COOT, PyMOL, or VMD. In this Perspective article, we outline how past developments in computer graphics and data visualization have expanded the understanding of biomolecular function, and we summarize recent advances that promise to further transform structural biology. We also highlight how progress in molecular graphics has been impeded by communication barriers between two communities: the computer scientists driving these advances, and the structural and computational biologists who stand to benefit. By pointing to canonical papers and explaining technical progress underlying new graphical developments in simple terms, we aim to improve communication between these communities; this, in turn, would help shape future developments in molecular graphics.

}, issn = {1878-4186}, doi = {10.1016/j.str.2019.09.001}, author = {Martinez, Xavier and Krone, Michael and Alharbi, Naif and Rose, Alexander S and Laramee, Robert S and O{\textquoteright}Donoghue, Sean and Marc Baaden and Chavent, Matthieu} } @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|2107, title = {Nonequilibrium atomistic molecular dynamics simulation of tubular nanomotor propelled by bubble propulsion}, journal = {The Journal of chemical physics}, volume = {151}, year = {2019}, pages = {024103}, author = {Man, Viet Hoang and Li, Mai Suan and Wang, Junmei and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2019, title = {Quantifying the Strength of a Salt Bridge by Neutron Scattering and Molecular Dynamics}, journal = {J. Phys. Chem. Lett.}, volume = {10}, year = {2019}, chapter = {3254}, doi = {10.1021/acs.jpclett.9b01309}, url = {https://pubs.acs.org/doi/10.1021/acs.jpclett.9b01309}, author = {P.E. Mason and P. Jungwirth and Elise Dubou{\'e}-Dijon} } @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|2063, title = {Residues in the fingers domain of the translesion DNA polymerase DinB enable its unique participation in error-prone double-strand break repair}, journal = {J Biol Chem}, volume = {294}, year = {2019}, month = {May}, pages = {7588-7600}, abstract = {

The evolutionarily conserved Escherichia coli translesion DNA polymerase IV (DinB) is one of three enzymes that can bypass potentially deadly DNA lesions on the template strand during DNA replication. Remarkably, however, DinB is the only known translesion DNA polymerase active in RecA-mediated strand exchange during error-prone double-strand break repair. In this process, a single-stranded DNA (ssDNA)-RecA nucleoprotein filament invades homologous dsDNA, pairing the ssDNA with the complementary strand in the dsDNA. When exchange reaches the 3\&$\#$39; end of the ssDNA, a DNA polymerase can add nucleotides onto the end, using one strand of dsDNA as a template and displacing the other. It is unknown what makes DinB uniquely capable of participating in this reaction. To explore this topic, we performed molecular modeling of DinB\&$\#$39;s interactions with the RecA filament during strand exchange, identifying key contacts made with residues in the DinB fingers domain. These residues are highly conserved in DinB, but not in other translesion DNA polymerases. Using a novel FRET-based assay, we found that DinB variants with mutations in these conserved residues are less effective at stabilizing RecA-mediated strand exchange than native DinB. Furthermore, these variants are specifically deficient in strand displacement in the absence of RecA filament. We propose that the amino acid patch of highly conserved residues in DinB-like proteins provides a mechanistic explanation for DinB\&$\#$39;s function in strand exchange and improves our understanding of recombination by providing evidence that RecA plays a role in facilitating DinB\&$\#$39;s activity during strand exchange.

}, keywords = {DinB, DNA damage, DNA polymerase, DNA polymerase IV, DNA repair, DNA synthesis, homologous recombination, RecA}, doi = {10.1074/jbc.RA118.006233}, author = {Tashjian, Tommy F and Danilowicz, Claudia and Molza, Anne-Elizabeth and Nguyen, Brian H and Chantal Pr{\'e}vost and Prentiss, Mara and Godoy, Veronica G} } @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} } @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|2112, title = {Breaking down cellulose fibrils with a mid-infrared laser}, journal = {Cellulose}, volume = {25}, year = {2018}, pages = {5553{\textendash}5568}, author = {Domin, Dominik and Man, Viet Hoang and Van-Oanh, Nguyen-Thi and Wang, Junmei and Kawasaki, Takayasu and Philippe Derreumaux and Phuong Hoang Nguyen} } @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|2093, title = {Dystrophin{\textquoteright}s central domain forms a complex filament that becomes disorganized by in-frame deletions.}, journal = {J Biol Chem}, volume = {293}, year = {2018}, month = {2018 05 04}, pages = {6637-6646}, abstract = {

Dystrophin, encoded by the gene, is critical for maintaining plasma membrane integrity during muscle contraction events. Mutations in the gene disrupting the reading frame prevent dystrophin production and result in severe Duchenne muscular dystrophy (DMD); in-frame internal deletions allow production of partly functional internally deleted dystrophin and result in less severe Becker muscular dystrophy (BMD). Many known BMD deletions occur in dystrophin\&$\#$39;s central domain, generally considered to be a monotonous rod-shaped domain based on the knowledge of spectrin family proteins. However, the effects caused by these deletions, ranging from asymptomatic to severe BMD, argue against the central domain serving only as a featureless scaffold. We undertook structural studies combining small-angle X-ray scattering and molecular modeling in an effort to uncover the structure of the central domain, as dystrophin has been refractory to characterization. We show that this domain appears to be a tortuous and complex filament that is profoundly disorganized by the most severe BMD deletion (loss of exons 45-47). Despite the preservation of large parts of the binding site for neuronal nitric oxide synthase (nNOS) in this deletion, computational approaches failed to recreate the association of dystrophin with nNOS. This observation is in agreement with a strong decrease of nNOS immunolocalization in muscle biopsies, a parameter related to the severity of BMD phenotypes. The structural description of the whole dystrophin central domain we present here is a first necessary step to improve the design of microdystrophin constructs toward the goal of a successful gene therapy for DMD.

}, keywords = {Binding Sites, Dystrophin, Exons, Gene Deletion, Humans, Molecular Docking Simulation, Muscular Dystrophy, Duchenne, Nitric Oxide Synthase Type I, Protein Domains, Reading Frames, Scattering, Small Angle, Solutions, X-Ray Diffraction}, issn = {1083-351X}, doi = {10.1074/jbc.M117.809798}, author = {Delalande, Olivier and Molza, Anne-Elisabeth and Dos Santos Morais, Raphael and Ch{\'e}ron, Ang{\'e}lique and Pollet, {\'E}meline and Raguenes-Nicol, C{\'e}line and Tascon, Christophe and Giudice, Emmanuel and Guilbaud, Marine and Nicolas, Aur{\'e}lie and Bondon, Arnaud and Leturcq, France and Nicolas F{\'e}rey and Marc Baaden and Perez, Javier and Roblin, Pierre and Pi{\'e}tri-Rouxel, France and Hubert, Jean-Fran{\c c}ois and Czjzek, Mirjam and Le Rumeur, Elisabeth} } @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|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|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} } @article {2018|2091, title = {MinOmics, an Integrative and Immersive Tool for Multi-Omics Analysis.}, journal = {J Integr Bioinform}, volume = {15}, year = {2018}, month = {2018 Jun 21}, abstract = {

Proteomic and transcriptomic technologies resulted in massive biological datasets, their interpretation requiring sophisticated computational strategies. Efficient and intuitive real-time analysis remains challenging. We use proteomic data on 1417 proteins of the green microalga Chlamydomonas reinhardtii to investigate physicochemical parameters governing selectivity of three cysteine-based redox post translational modifications (PTM): glutathionylation (SSG), nitrosylation (SNO) and disulphide bonds (SS) reduced by thioredoxins. We aim to understand underlying molecular mechanisms and structural determinants through integration of redox proteome data from gene- to structural level. Our interactive visual analytics approach on an 8.3 m2 display wall of 25 MPixel resolution features stereoscopic three dimensions (3D) representation performed by UnityMol WebGL. Virtual reality headsets complement the range of usage configurations for fully immersive tasks. Our experiments confirm that fast access to a rich cross-linked database is necessary for immersive analysis of structural data. We emphasize the possibility to display complex data structures and relationships in 3D, intrinsic to molecular structure visualization, but less common for omics-network analysis. Our setup is powered by MinOmics, an integrated analysis pipeline and visualization framework dedicated to multi-omics analysis. MinOmics integrates data from various sources into a materialized physical repository. We evaluate its performance, a design criterion for the framework.

}, keywords = {Algal Proteins, Chlamydomonas reinhardtii, Computer Graphics, Imaging, Three-Dimensional, Models, Structural, Oxidation-Reduction, Protein Conformation, Protein Interaction Maps, Protein Processing, Post-Translational, Proteome, Proteomics, Software, Virtual Reality}, issn = {1613-4516}, doi = {10.1515/jib-2018-0006}, author = {Maes, Alexandre and Martinez, Xavier and Druart, Karen and Laurent, Benoist and Gu{\'e}gan, Sean and Marchand, Christophe H and Lemaire, St{\'e}phane D and Marc Baaden} } @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|2111, title = {Molecular mechanism of the cell membrane pore formation induced by bubble stable cavitation}, journal = {The Journal of Physical Chemistry B}, volume = {123}, year = {2018}, pages = {71{\textendash}78}, author = {Man, Viet Hoang and Truong, Phan Minh and Li, Mai Suan and Wang, Junmei and Van-Oanh, Nguyen-Thi and Philippe Derreumaux and Phuong Hoang Nguyen} } @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|2114, title = {Rayleigh-Plesset equation of the bubble stable cavitation in water: A nonequilibrium all-atom molecular dynamics simulation study}, journal = {The Journal of Chemical Physics}, volume = {148}, year = {2018}, pages = {094505}, author = {Man, Viet Hoang and Li, Mai Suan and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2018, title = {RecA requires two molecules of Mg2+ ions for its optimal strand exchange activity in vitro}, journal = {Nucleic Acids Res}, volume = {ahead of print}, year = {2018}, month = {Jan}, abstract = {

Mg2+ ion stimulates the DNA strand exchange reaction catalyzed by RecA, a key step in homologous recombination. To elucidate the molecular mechanisms underlying the role of Mg2+ and the strand exchange reaction itself, we investigated the interaction of RecA with Mg2+ and sought to determine which step of the reaction is affected. Thermal stability, intrinsic fluorescence, and native mass spectrometric analyses of RecA revealed that RecA binds at least two Mg2+ ions with KD \‚{\^a}{\`a} 2 mM and 5 mM. Deletion of the C-terminal acidic tail of RecA made its thermal stability and fluorescence characteristics insensitive to Mg2+ and similar to those of full-length RecA in the presence of saturating Mg2+. These observations, together with the results of a molecular dynamics simulation, support the idea that the acidic tail hampers the strand exchange reaction by interacting with other parts of RecA, and that binding of Mg2+ to the tail prevents these interactions and releases RecA from inhibition. We observed that binding of the first Mg2+ stimulated joint molecule formation, whereas binding of the second stimulated progression of the reaction. Thus, RecA is actively involved in the strand exchange step as well as bringing the two DNAs close to each other.

}, doi = {10.1093/nar/gky048}, author = {Kim, Raeyeong and Kanamaru, Shuji and Mikawa, Tsutomu and Chantal Pr{\'e}vost and Ishii, Kentaro and Ito, Kentaro and Uchiyama, Susumu and Oda, Masayuki and Iwasaki, Hiroshi and Kim, Seog K and Takahashi, Masayuki} } @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|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|2032, title = {Conformational Ensembles of the Wild-Type and S8C Aβ1-42 Dimers.}, journal = {J Phys Chem B}, volume = {121}, year = {2017}, month = {2017 Mar 23}, pages = {2434-2442}, abstract = {

We characterized the dimer of the amyloid-β wild-type (WT) peptide, Aβ, of 42 residues and its disulfide-bond-locked double mutant (S8C) by replica exchange molecular dynamics simulations. Aβ dimers are known to be the smallest toxic species in Alzheimer\&$\#$39;s disease, and the S8C mutant has been shown experimentally to form an exclusive homogeneous and neurotoxic dimer. Our 50 μs all-atom simulations reveal similar secondary structures and collision cross-sections but very different intramolecular and intermolecular conformations upon double S8C mutation. Both dimers are very dynamic with hundreds of free-energy minima that differ from the U-shape and S-shape conformations of the peptides in the fibrils. The only common structural feature, shared by both species with a probability of 4\% in WT and 12\% in S8C-S8C, is a three-stranded β-sheet spanning the 17-23, 29-36, and 39-41 residues, which does not exist in the Aβ40 WT dimers.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b00267}, author = {Man, Viet Hoang and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2017|2031, title = {High-Resolution Structures of the Amyloid-β 1-42 Dimers from the Comparison of Four Atomistic Force Fields.}, journal = {J Phys Chem B}, volume = {121}, year = {2017}, month = {2017 Jun 22}, pages = {5977-5987}, abstract = {

The dimer of the amyloid-β peptide Aβ of 42 residues is the smallest toxic species in Alzheimer\&$\#$39;s disease, but its equilibrium structures are unknown. Here we determined the equilibrium ensembles generated by the four atomistic OPLS-AA, CHARMM22*, AMBER99sb-ildn, and AMBERsb14 force fields with the TIP3P water model. On the basis of 144 μs replica exchange molecular dynamics simulations (with 750 ns per replica), we find that the four force fields lead to random coil ensembles with calculated cross-collision sections, hydrodynamics properties, and small-angle X-ray scattering profiles independent of the force field. There are, however, marked differences in secondary structure, with the AMBERsb14 and CHARMM22* ensembles overestimating the CD-derived helix content, and the OPLS-AA and AMBER99sb-ildn secondary structure contents in agreement with CD data. Also the intramolecular beta-hairpin content spanning residues 17-21 and 30-36 varies between 1.5\% and 13\%. Overall, there are significant differences in tertiary and quaternary conformations among all force fields, and the key finding, irrespective of the force field, is that the dimer is stabilized by nonspecific interactions, explaining therefore its possible transient binding to multiple cellular partners and, in part, its toxicity.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b04689}, author = {Man, Viet Hoang and Phuong Hoang Nguyen and Philippe Derreumaux} } @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|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|2096, title = {String method solution of the gating pathways for a pentameric ligand-gated ion channel.}, journal = {Proc Natl Acad Sci U S A}, volume = {114}, year = {2017}, month = {2017 05 23}, pages = {E4158-E4167}, abstract = {

Pentameric ligand-gated ion channels control synaptic neurotransmission by converting chemical signals into electrical signals. Agonist binding leads to rapid signal transduction via an allosteric mechanism, where global protein conformational changes open a pore across the nerve cell membrane. We use all-atom molecular dynamics with a swarm-based string method to solve for the minimum free-energy gating pathways of the proton-activated bacterial GLIC channel. We describe stable wetted/open and dewetted/closed states, and uncover conformational changes in the agonist-binding extracellular domain, ion-conducting transmembrane domain, and gating interface that control communication between these domains. Transition analysis is used to compute free-energy surfaces that suggest allosteric pathways; stabilization with pH; and intermediates, including states that facilitate channel closing in the presence of an agonist. We describe a switching mechanism that senses proton binding by marked reorganization of subunit interface, altering the packing of β-sheets to induce changes that lead to asynchronous pore-lining M2 helix movements. These results provide molecular details of GLIC gating and insight into the allosteric mechanisms for the superfamily of pentameric ligand-gated channels.

}, keywords = {Computer Simulation, Ligand-Gated Ion Channels, Models, Biological, Models, Chemical}, issn = {1091-6490}, doi = {10.1073/pnas.1617567114}, author = {Lev, Bogdan and Murail, Samuel and Poitevin, Fr{\'e}d{\'e}ric and Cromer, Brett A and Marc Baaden and Delarue, Marc and Allen, Toby W} } @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|2036, title = {VLITL is a major cross-β-sheet signal for fibrinogen Aα-chain frameshift variants.}, journal = {Blood}, volume = {130}, year = {2017}, month = {2017 12 21}, pages = {2799-2807}, abstract = {

The first case of hereditary fibrinogen Aα-chain amyloidosis was recognized \>20 years ago, but disease mechanisms still remain unknown. Here we report detailed clinical and proteomics studies of a French kindred with a novel amyloidogenic fibrinogen Aα-chain frameshift variant, Phe521Leufs, causing a severe familial form of renal amyloidosis. Next, we focused our investigations to elucidate the molecular basis that render this Aα-chain variant amyloidogenic. We show that a 49-mer peptide derived from the C-terminal part of the Phe521Leufs chain is deposited as fibrils in the patient\&$\#$39;s kidneys, establishing that only a small portion of Phe521Leufs directly contributes to amyloid formation in vivo. In silico analysis indicated that this 49-mer Aα-chain peptide contained a motif (VLITL), with a high intrinsic propensity for β-aggregation at residues 44 to 48 of human renal fibrils. To experimentally verify the amyloid propensity of VLITL, we generated synthetic Phe521Leufs-derived peptides and compared their capacity for fibril formation in vitro with that of their VLITL-deleted counterparts. We show that VLITL forms typical amyloid fibrils in vitro and is a major signal for cross-β-sheet self-association of the 49-mer Phe521Leufs peptide identified in vivo, whereas its absence abrogates fibril formation. This study provides compelling evidence that VLITL confers amyloidogenic properties to Aα-chain frameshift variants, yielding a previously unknown molecular basis for the pathogenesis of Aα-chain amyloidosis.

}, keywords = {Amino Acid Motifs, Amino Acid Sequence, Amyloid, Amyloidosis, Familial, Fibrinogen, Frameshift Mutation, Humans, Kidney, Protein Conformation, beta-Strand}, issn = {1528-0020}, doi = {10.1182/blood-2017-07-796185}, author = {Garnier, Cyrille and Briki, Fatma and Nedelec, Brigitte and Le Pogamp, Patrick and Dogan, Ahmet and Rioux-Leclercq, Nathalie and Goude, Renan and Beugnet, Caroline and Martin, Laurent and Delpech, Marc and Bridoux, Frank and Grateau, Gilles and Doucet, Jean and Philippe Derreumaux and Valleix, Sophie} } @article {2017|2043, title = {Weak nanoscale chaos and anomalous relaxation in DNA}, journal = {Phys. Rev. E}, volume = {95}, year = {2017}, pages = {062417}, doi = {https://doi.org/10.1103/PhysRevE.95.062417}, author = {Alexey K. Mazur} } @article {2017|2042, title = {What Can Human-Guided Simulations Bring to RNA Folding?}, journal = {Biophys J}, volume = {113}, year = {2017}, month = {2017 Jul 25}, pages = {302-312}, abstract = {

Inspired by the recent success of scientific-discovery games for predicting protein tertiary and RNA secondary structures, we have developed an open software for coarse-grained RNA folding simulations, guided by human intuition. To determine the extent to which interactive simulations can accurately predict 3D RNA structures of increasing complexity and lengths (four RNAs with 22-47 nucleotides), an interactive experiment was conducted with 141 participants who had very little knowledge of nucleic acids systems and computer simulations, and had received only a brief description of the important forces stabilizing RNA structures. Their structures and full trajectories have been analyzed statistically and compared to standard replica exchange molecular dynamics simulations. Our analyses show that participants gain easily chemical intelligence to fold simple and nontrivial topologies, with little computer time, and this result opens the door for the use of human-guided simulations to RNA folding. Our experiment shows that interactive simulations have better chances of success when the user widely explores the conformational space. Interestingly, providing on-the-fly feedback of the root mean square deviation with respect to the experimental structure did not improve the quality of the proposed models.

}, keywords = {Access to Information, Computer Simulation, Feedback, Psychological, Humans, Internet, Models, Genetic, Models, Molecular, RNA, RNA Folding, Software, Solvents}, issn = {1542-0086}, doi = {10.1016/j.bpj.2017.05.047}, author = {Mazzanti, Liuba and Doutreligne, S{\'e}bastien and Gageat, Cedric and Philippe Derreumaux and Antoine Taly and Marc Baaden and Pasquali, Samuela} } @article {2016|2115, title = {Aβ41 Aggregates More Like Aβ40 than Like Aβ42: In Silico and in Vitro Study}, journal = {The Journal of Physical Chemistry B}, volume = {120}, year = {2016}, pages = {7371{\textendash}7379}, author = {Nguyen, Hoang Linh and Thi Minh Thu, Tran and Truong, Phan Minh and Lan, Pham Dang and Man, Viet Hoang and Phuong Hoang Nguyen and Tu, Ly Anh and Chen, Yi-Cheng and Li, Mai Suan} } @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|1742, title = {Homologous Pairing between Long DNA Double Helices}, journal = {Phys. Rev. Lett.}, volume = {116}, year = {2016}, pages = {158101}, author = {Alexey K Mazur} } @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|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|1750, title = {Non-equivalent binding sites for Abeta1-40 on PrP determine the oligomerisation pathway}, journal = {Prion}, volume = {10}, number = {1}, year = {2016}, pages = {S40}, issn = {1933-6896}, author = {Grznarova, Katarina and Torrent, Joan and Munoz-Montesino, Carola and Nasica, Jessica and Philippe Derreumaux and Beringue, Vincent and Deslys, Jean-Philippe and Rezaei, Human} } @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|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 {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|1679, title = {Conformational ensembles and sampled landscapes: analysis and comparison}, journal = {J. Comp. Chem.}, volume = {36}, year = {2015}, pages = {1213{\textendash}31}, author = {Fr{\'e}d{\'e}ric Cazals and A Roth and T Dreyfus and D Mazauric and Charles H. Robert} } @article {2015|1713, title = {Folding Atomistic Proteins in Explicit Solvent Using Simulated Tempering}, journal = {J. Phys. Chem. B}, volume = {119}, number = {23}, year = {2015}, month = {jun}, pages = {6941{\textendash}6951}, author = {Zhang, Tong and Phuong Hoang Nguyen and Nasica-Labouze, Jessica and Mu, Yuguang and Philippe Derreumaux} } @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|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|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|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 {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.} } @article {2014|1380, title = {Atomic and Dynamic Insights into the Beneficial Effect of the 1,4-Naphthoquinon-2-yl-L-tryptophan Inhibitor on Alzheimer{\textquoteright}s A beta 1-42 Dimer in Terms of Aggregation and Toxicity}, journal = {Acs Chem. Neurosci.}, volume = {5}, number = {2}, year = {2014}, month = {feb}, pages = {148{\textendash}159}, author = {Zhang, Tong and Xu, Weixin and Mu, Yuguang and Philippe Derreumaux} } @article {2014|1945, title = {Atomic force microscopy study of DNA flexibility on short length scales: Smooth bending versus kinking}, journal = {Nucleic. Acids. Res.}, volume = {42}, year = {2014}, pages = {14006{\textendash}14012}, author = {Alexey K Mazur and Mounir Maaloum} } @article {2014|1951, title = {DNA flexibility on short length scales probed by atomic force microscopy}, journal = {Phys. Rev. Lett.}, volume = {112}, year = {2014}, pages = {068104}, author = {Alexey K Mazur and Mounir Maaloum} } @article {2014|1411, title = {{I}nnovative interactive flexible docking method for multi-scale reconstruction elucidates dystrophin molecular assembly}, journal = {Faraday Discuss.}, volume = {169}, year = {2014}, note = {[DOI:\href{http://dx.doi.org/10.1039/c3fd00134b}{10.1039/c3fd00134b}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25340652}{25340652}]}, pages = {45{\textendash}62}, author = {Molza, A. E and Nicolas F{\'e}rey and Czjzek, M and Le Rumeur, E and Hubert, J. F and Tek, A and Laurent, B and Marc Baaden and Delalande, O.} } @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|1772, title = {INRIA Tech Report: Conformational ensembles and sampled landscapes: analysis and comparison.}, year = {2014}, author = {Fr{\'e}d{\'e}ric Cazals and T. Dreyfus and D. Mazauric and A. Roth and Charles H. Robert} } @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|1717, title = {Lipid concentration and molar ratio boundaries for the use of isotropic bicelles.}, journal = {Langmuir}, volume = {30}, number = {21}, year = {2014}, month = {jun}, pages = {6162{\textendash}6170}, publisher = {Department of Chemistry, Universit{\'e} du Qu{\'e}bec {\`a} Montr{\'e}al and Centre Qu{\'e}b{\'e}cois sur les Mat{\'e}riaux Fonctionnels , P.O. Box 8888, Downtown Station, Montreal, Canada H3C 3P8.}, abstract = {Bicelles are model membranes generally made of long-chain dimyristoylphosphatidylcholine (DMPC) and short-chain dihexanoyl-PC (DHPC). They are extensively used in the study of membrane interactions and structure determination of membrane-associated peptides, since their composition and morphology mimic the widespread PC-rich natural eukaryotic membranes. At low DMPC/DHPC (q) molar ratios, fast-tumbling bicelles are formed in which the DMPC bilayer is stabilized by DHPC molecules in the high-curvature rim region. Experimental constraints imposed by techniques such as circular dichroism, dynamic light scattering, or microscopy may require the use of bicelles at high dilutions. Studies have shown that such conditions induce the formation of small aggregates and alter the lipid-to-detergent ratio of the bicelle assemblies. The objectives of this work were to determine the exact composition of those DMPC/DHPC isotropic bicelles and study the lipid miscibility. This was done using (31)P nuclear magnetic resonance (NMR) and exploring a wide range of lipid concentrations (2-400 mM) and q ratios (0.15-2). Our data demonstrate how dilution modifies the actual DMPC/DHPC molar ratio in the bicelles. Care must be taken for samples with a total lipid concentration <=250 mM and especially at q \~{} 1.5-2, since moderate dilutions could lead to the formation of large and slow-tumbling lipid structures that could hinder the use of solution NMR methods, circular dichroism or dynamic light scattering studies. Our results, supported by infrared spectroscopy and molecular dynamics simulations, also show that phospholipids in bicelles are largely segregated only when q > 1. Boundaries are presented within which control of the bicelles{\textquoteright} q ratio is possible. This work, thus, intends to guide the choice of q ratio and total phospholipid concentration when using isotropic bicelles.}, keywords = {chemistry, Circular Dichroism, Detergents, Dimyristoylphosphatidylcholine, Fourier Transform Infrared, Light, Lipid Bilayers, Magnetic Resonance Spectroscopy, Materials Testing, Micelles, Molecular Dynamics Simulation, Phospholipid Ethers, Phospholipids, Radiation, Scattering, Solutions, Spectroscopy, Temperature}, doi = {10.1021/la5004353}, author = {Beaugrand, Ma\"{\i}wenn and Arnold, Alexandre A. and J{\'e}r{\^o}me H{\'e}nin and Warschawski, Dror E. and Williamson, Philip T F. and Marcotte, Isabelle} } @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 {2013|1403, title = {{C}oarse-grain modelling of protein-protein interactions}, journal = {Curr. Opin. Struct. Biol.}, volume = {23}, number = {6}, year = {2013}, pages = {878{\textendash}886}, author = {Marc Baaden and Marrink, S. J.} } @article {2013|1743, title = {Comment on {\textquoteright}Length scale dependence of DNA mechanical properties{\textquoteright}}, journal = {Phys. Rev. Lett.}, volume = {111}, year = {2013}, pages = {179801}, author = {Alexey K Mazur} } @article {2013|1523, title = {Comment on {\textquoteleft}{\textquoteleft}Length Scale Dependence of DNA Mechanical Properties{{\textquoteright}{\textquoteright}}}, journal = {Phys. Rev. Lett.}, volume = {111}, number = {17}, year = {2013}, month = {oct}, author = {Alexey K Mazur} } @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|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} } @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|1925, title = {Molecular Mechanism of the Inhibition of EGCG on the Alzheimer A beta(1-42) Dimer}, journal = {J. Phys. Chem. B}, volume = {117}, number = {15}, year = {2013}, month = {apr}, pages = {3993{\textendash}4002}, doi = {10.1021/jp312573y}, author = {Zhang, Tong and Zhang, Jian and Philippe Derreumaux and Mu, Yuguang} } @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|1688, title = {On the origin of thermal untwisting of DNA}, journal = {J. Phys. Chem. B}, volume = {117}, year = {2013}, pages = {1857{\textendash}1861}, author = {Alexey K Mazur} } @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|1814, title = {Towards Morse theory for point cloud data.}, journal = {Inria Tech Reports}, number = {8331}, year = {2013}, publisher = {Inria}, url = {http://hal.inria.fr/hal-00848753}, author = {F. Cazals and C. Mueller and C. Robert and A. Roth} } @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} } @inbook {2012|1575, title = {Advances in Human-Protein Interaction - Interactive And Immersive Molecular Simulations}, year = {2012}, publisher = {Intech, Croatia}, organization = {Intech, Croatia}, chapter = {Protein Interaction / Book 2}, author = {A. Tek and B. Laurent and M. Piuzzi and Z. Lu and Marc Baaden and O. Delalande and Matthieu Chavent and Nicolas F{\'e}rey and C. Martin and L. Piccinali and B. Katz and P. Bourdot and Ludovic Autin}, editor = {W. Cai and H. Hong} } @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|1922, title = {Distinct Dimerization for Various Alloforms of the Amyloid-Beta Protein: A beta(1-40), A beta(1-42), and A beta(1-40)(D23N)}, journal = {J. Phys. Chem. B}, volume = {116}, number = {13}, year = {2012}, month = {apr}, pages = {4043{\textendash}4055}, doi = {10.1021/jp2126366}, author = {Cote, Sebastien and Laghaei, Rozita and Philippe Derreumaux and Mousseau, Normand} } @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|1756, title = {Involvement of the cysteine-rich head domain in activation and desensitization of the P2X1 receptor}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {28}, year = {2012}, pages = {11396{\textendash}11401}, publisher = {National Acad Sciences}, author = {L{\"o}rinczi, {\'E}va and Bhargava, Yogesh and Marino, Stephen F and Antoine Taly and Kaczmarek-H{\'a}jek, Karina and Barrantes-Freer, Alonso and Dutertre, S{\'e}bastien and Grutter, Thomas and Rettinger, J{\"u}rgen and Nicke, Annette} } @article {2012|1546, title = {Modeling complex biological systems: From solution chemistry to membranes and channels}, journal = {Pure Appl. Chem.}, volume = {ASAP}, year = {2012}, month = {nov}, doi = {10.1351/PAC-CON-12-04-10}, author = {B. Laurent and S. Murail and F. Da Silva and P.-J. Corringer and Marc Baaden} } @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|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|1921, title = {Structures of A beta 17-42 Trimers in Isolation and with Five Small-Molecule Drugs Using a Hierarchical Computational Procedure}, journal = {J. Phys. Chem. B}, volume = {116}, number = {29, SI}, year = {2012}, month = {jul}, pages = {8412{\textendash}8422}, doi = {10.1021/jp2118778}, author = {Y Chebaro and Jiang, Ping and Zang, Tong and Mu, Yuguang and Phuong Hoang Nguyen and Mousseau, Normand and Philippe Derreumaux} } @article {2012|1805, title = {{T}ightening of the {A}{T}{P}-binding sites induces the opening of {P}2{X} receptor channels}, journal = {Embo J.}, volume = {31}, number = {9}, year = {2012}, month = {may}, pages = {2134{\textendash}2143}, author = {Jiang, R. and Antoine Taly and Lemoine, D. and Martz, A. and Cunrath, O. and Grutter, T.} } @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|1740, title = {Torque transfer coefficient in DNA under torsional stress}, journal = {Phys. Rev. E}, volume = {86}, year = {2012}, pages = {011914}, author = {Alexey K Mazur} } @conference {2011|1611, title = {Characterization of the Aggregation Pathway for a 20-mer of GNNQQNY using Coarse-Grained and All-Atom Representations}, booktitle = {Biophys. J.}, volume = {100}, number = {3}, year = {2011}, month = {feb}, pages = {Biophys Soc}, author = {Nasica-Labouze, Jessica and Meli, Massimiliano and Philippe Derreumaux and Colombo, Giorgio and Mousseau, Normand} } @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|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|1857, title = {{D}iscrimination of agonists versus antagonists of nicotinic ligands based on docking onto {A}{C}h{B}{P} structures}, journal = {J. Mol. Graph. Model.}, volume = {30}, year = {2011}, month = {sep}, pages = {100{\textendash}109}, author = {Antoine Taly and Colas, C. and Malliavin, T. and Blondel, A. and Nilges, M. and Corringer, P. J. and Joseph, D.} } @article {2011|1890, title = {Distinct Morphologies for Amyloid Beta Protein Monomer: A beta(1-40), A beta(1-42), and A beta(1-40)(D23N)}, journal = {J. Chem. Theory Comput.}, volume = {7}, number = {8}, year = {2011}, month = {aug}, pages = {2584{\textendash}2592}, doi = {10.1021/ct1006967}, author = {Cote, Sebastien and Philippe Derreumaux and Mousseau, Normand} } @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|1966, title = {Intrinsic Determinants of A beta(12-24) pH-Dependent Self-Assembly Revealed by Combined Computational and Experimental Studies}, journal = {Plos One}, volume = {6}, number = {9}, year = {2011}, month = {sep}, pages = {e24329}, doi = {10.1371/journal.pone.0024329}, author = {Xu, Weixin and Zhang, Ce and Philippe Derreumaux and Graslund, Astrid and Morozova-Roche, Ludmilla and Mu, Yuguang} } @article {2011|1741, title = {Local elasticity of strained DNA studied by all-atom simulations}, journal = {Phys. Rev. E}, volume = {84}, year = {2011}, pages = {021903}, author = {Alexey K Mazur} } @article {2011|1962, title = {A Multiscale Approach to Characterize the Early Aggregation Steps of the Amyloid-Forming Peptide GNNQQNY from the Yeast Prion Sup-35}, journal = {Plos Comput. Biol.}, volume = {7}, number = {5}, year = {2011}, month = {may}, pages = {e1002051}, doi = {10.1371/journal.pcbi.1002051}, author = {Nasica-Labouze, Jessica and Meli, Massimiliano and Philippe Derreumaux and Colombo, Giorgio and Mousseau, Normand} } @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|1748, title = {Optimizing the design of oligonucleotides for homology directed gene targeting}, journal = {Plos One}, volume = {6}, year = {2011}, pages = {e14795}, abstract = {

BACKGROUND: Gene targeting depends on the ability of cells to use homologous recombination to integrate exogenous DNA into their own genome. A robust mechanistic model of homologous recombination is necessary to fully exploit gene targeting for therapeutic benefit. METHODOLOGY/PRINCIPAL FINDINGS: In this work, our recently developed numerical simulation model for homology search is employed to develop rules for the design of oligonucleotides used in gene targeting. A Metropolis Monte-Carlo algorithm is used to predict the pairing dynamics of an oligonucleotide with the target double-stranded DNA. The model calculates the base-alignment between a long, target double-stranded DNA and a probe nucleoprotein filament comprised of homologous recombination proteins (Rad51 or RecA) polymerized on a single strand DNA. In this study, we considered different sizes of oligonucleotides containing 1 or 3 base heterologies with the target; different positions on the probe were tested to investigate the effect of the mismatch position on the pairing dynamics and stability. We show that the optimal design is a compromise between the mean time to reach a perfect alignment between the two molecules and the stability of the complex. CONCLUSION AND SIGNIFICANCE: A single heterology can be placed anywhere without significantly affecting the stability of the triplex. In the case of three consecutive heterologies, our modeling recommends using long oligonucleotides (at least 35 bases) in which the heterologous sequences are positioned at an intermediate position. Oligonucleotides should not contain more than 10\% consecutive heterologies to guarantee a stable pairing with the target dsDNA. Theoretical modeling cannot replace experiments, but we believe that our model can considerably accelerate optimization of oligonucleotides for gene therapy by predicting their pairing dynamics with the target dsDNA.

}, doi = {10.1371/journal.pone.0014795}, author = {Min{\'e}-Hattab, Judith and Fleury, Genevi{\`e}ve and Chantal Pr{\'e}vost and Dutreix, Marie and Viovy, Jean-Louis} } @inbook {2011|1417, title = {Receptor Flexibility in Ligand Docking and Virtual Screening.}, booktitle = {In-silico lead discovery}, year = {2011}, publisher = {Bentham Science Publishers}, organization = {Bentham Science Publishers}, author = {Maria A. Miteva and Charles H. Robert and J. D. Marechal and David Perahia} } @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|1782, title = {Simulation of the Oligomerization Pathway for Different Alloforms of the Amyloid Beta Protein Related to Alzheimer{\textquoteright}s Disease}, journal = {Biophys. J.}, volume = {100}, number = {3, 1}, year = {2011}, note = {55th Annual Meeting of the Biophysical-Society, Baltimore, MD, MAR 05-09, 2011}, month = {feb}, pages = {401}, author = {Cote, Sebastien and Laghaei, Rozita and Philippe Derreumaux and Mousseau, Normand} } @article {2010|1950, title = {Anharmonic torsional stiffness of DNA revealed under small external torques}, journal = {Phys. Rev. Lett.}, volume = {105}, year = {2010}, pages = {018102}, author = {Alexey K Mazur} } @article {2010|1736, title = {Consensus {M}odes, a robust description of protein collective motions from multiple-minima normal mode analysis{\textendash}application to the {HIV}-1 protease.}, journal = {Phys. Chem. Chem. Phys.}, volume = {12}, year = {2010}, month = {mar}, pages = {2850{\textendash}2859}, abstract = {

Protein flexibility is essential for enzymatic function, ligand binding, and protein-protein or protein-nucleic acid interactions. Normal mode analysis has increasingly been shown to be well suited for studying such flexibility, as it can be used to identify favorable structural deformations that correspond to functional motions. However, normal modes are strictly relevant to a single structure, reflecting a particular minimum on a complex energy surface, and are thus susceptible to artifacts. We describe a new theoretical framework for determining \"consensus\" normal modes from a set of related structures, such as those issuing from a short molecular dynamics simulation. This approach is more robust than standard normal mode analysis, and provides higher collectivity and symmetry properties. In an application to HIV-1 protease, the low-frequency consensus modes describe biologically relevant motions including flap opening and closing that can be used in interpreting structural changes accompanying the binding of widely differing inhibitors.

}, doi = {10.1039/b919148h}, author = {Paulo R. Batista and Charles H. Robert and Jean-Didier Mar{\'e}chal and M{\'e}riam Ben Hamida{\textendash}Reba\"{\i} and Paulo Pascutti and Paulo M. Bisch and David P. Perahia} } @article {2010|1901, title = {A Fast Method for Large-Scale De Novo Peptide and Miniprotein Structure Prediction}, journal = {J. Comput. Chem.}, volume = {31}, number = {4}, year = {2010}, month = {mar}, pages = {726{\textendash}738}, doi = {10.1002/jcc.21365}, author = {Maupetit, Julien and Philippe Derreumaux and Pierre Tuffery} } @article {2010|2007, title = {{A} putative extracellular salt bridge at the subunit interface contributes to the ion channel function of the {A}{T}{P}-gated {P}2{X}2 receptor}, journal = {J. Biol. Chem.}, volume = {285}, number = {21}, year = {2010}, month = {may}, pages = {15805{\textendash}15815}, publisher = {American Society for Biochemistry and Molecular Biology}, author = {Jiang, R. and Martz, A. and Gonin, S. and Antoine Taly and de Carvalho, L. P. and Grutter, T.} } @article {2010, title = {The VLITL aggregation-prone motif might trigger amyloid fibril formation of fibrinogen A alpha-chain frameshift variants in vivo}, journal = {Amyloid-journal of Protein Folding Disorders}, volume = {17}, number = {Suppl. 1}, year = {2010}, note = {12th International Symposium on Amyloidosis from Molecular Mechanisms Toward the Cure of Systemic Amyloidoses, Rome, ITALY, APR 18-21, 2010}, pages = {96{\textendash}97}, author = {Valleix, S. and Philippe Derreumaux and Garnier, C. and Briki, F. and Boimard, M. and Doucet, J. and Rioux-Leclercq, N. and Martin, L. and Grateau, G. and Delpech, M. and Le Pogamp, P.} } @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 {2009|1947, title = {Analysis of accordion DNA stretching revealed by the gold cluster ruler}, journal = {Phys. Rev. E}, volume = {80}, year = {2009}, pages = {010901}, author = {Alexey K Mazur} } @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|1394, title = {Disulfide bond substitution by directed evolution in an engineered binding-protein scaffold.}, journal = {Chembiochem}, volume = {10}, year = {2009}, pages = {1349{\textendash}1359}, author = {Antoine Drevelle and Agathe Urvoas and M{\'e}riam Ben Hamida-Rebai and G{\'e}rard Van Vooren and Magali Nicaise and Marie Valerio-Lepiniec and Michel Desmadril and Charles H. Robert and Philippe Minard} } @article {2009|1436, title = {A fast method for large-scale De Novo peptide and miniprotein structure prediction.}, journal = {J. Comput. Chem.}, year = {2009}, month = {jun}, doi = {10.1002/jcc.21365}, author = {Julien Maupetit and Philippe Derreumaux and Pierre Tuffery} } @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|1863, title = {Kinetic and thermodynamic DNA elasticity at micro- and mesoscopic scales}, journal = {J. Phys. Chem. B}, volume = {113}, year = {2009}, pages = {2077{\textendash}2089}, author = {Alexey K Mazur} } @article {2009|1850, title = {Modeling DNA dynamics under steady deforming forces and torques}, journal = {J. Chem. Theory Comput.}, volume = {5}, year = {2009}, pages = {2149{\textendash}2157}, author = {Alexey K Mazur} } @article {2009|1438, title = {{A}n optimized extended {D}{N}{A} kappa {B} site that enhances plasmid {D}{N}{A} nuclear import and gene expression}, journal = {J. Gene Med.}, volume = {11}, year = {2009}, month = {may}, pages = {401{\textendash}411}, author = {Goncalves, C. and Ardourel, M. Y. and Decoville, M. and Breuzard, G. and Midoux, P. and Hartmann, B. and Pichon, C.} } @article {2009|1384, title = {New Insight into the interaction between erbin and smad3: a non-classical binding interface for the erbin PDZ domain}, journal = {Biochem. Biophys. Res. Commun.}, volume = {378}, number = {3}, year = {2009}, pages = {360{\textendash}365}, author = {N Deliot and Matthieu Chavent and C Nourry and P Lecine and C Arnaud and A Hermant and B Maigret and J.-P. Borg} } @article {2009|1521, title = {Numerical studies of Lifshitz interactions between dielectrics}, journal = {Phys. Rev. A}, volume = {79}, year = {2009}, pages = {020102(R)}, author = {S. Pasquali and A.C. Maggs} } @article {2009|1942, title = {PEP-FOLD: an online resource for de novo peptide structure prediction.}, journal = {Nucleic Acids Res.}, volume = {37}, number = {Web Server issue}, year = {2009}, month = {jul}, pages = {W498{\textendash}W503}, keywords = {Algorithms, Internet, Models, Molecular, Peptides, Protein, Protein Conformation, Reproducibility of Results, Sequence Analysis, Software, User-Computer Interface}, doi = {10.1093/nar/gkp323}, author = {Julien Maupetit and Philippe Derreumaux and Pierre Tuffery} } @article {2009|1734, title = {PEP-FOLD: an online resource for de novo peptide structure prediction}, journal = {Nucleic Acids Res.}, volume = {37}, year = {2009}, month = {jul}, pages = {W498-W503}, doi = {10.1093/nar/gkp323}, author = {Maupetit, Julien and Philippe Derreumaux and Pierre Tuffery} } @article {2009|1830, title = {Replica exchange molecular dynamics simulations of coarse-grained proteins in implicit solvent.}, journal = {J. Phys. Chem. B}, volume = {113}, number = {1}, year = {2009}, month = {jan}, pages = {267{\textendash}274}, keywords = {Amino Acid Sequence, Computer Simulation, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Peptides, Protein Folding, Protein Structure, Proteins, Secondary, Solvents, Temperature, Thermodynamics}, doi = {10.1021/jp805309e}, author = {Y Chebaro and Xiao Dong and Rozita Laghaei and Philippe Derreumaux and Normand Mousseau} } @article {2009|1779, title = {Role of nucleic acid binding in Sir3p-dependent interactions with chromatin fibers.}, journal = {Biochemistry}, volume = {48}, number = {2}, year = {2009}, month = {jan}, pages = {276{\textendash}288}, publisher = {Department of Biological Sciences and Cell Differentiation and Development Center, Marshall University, Huntington, West Virginia 25755, USA.}, abstract = {

Recent studies of the mechanisms involved in the regulation of gene expression in eukaryotic organisms depict a highly complex process requiring a coordinated rearrangement of numerous molecules to mediate DNA accessibility. Silencing in Saccharomyces cerevisiae involves the Sir family of proteins. Sir3p, originally described as repressing key areas of the yeast genome through interactions with the tails of histones H3 and H4, appears to have additional roles in that process, including involvement with a DNA binding component. Our in vitro studies focused on the characterization of Sir3p-nucleic acid interactions and their biological functions in Sir3p-mediated silencing using binding assays, EM imaging, and theoretical modeling. Our results suggest that the initial Sir3p recruitment is partially DNA-driven, highly cooperative, and dependent on nucleosomal features other than histone tails. The initial step appears to be rapidly followed by the spreading of silencing using linker DNA as a track.

}, doi = {10.1021/bi801705g}, author = {Nicholas L Adkins and Steve J McBryant and Cotteka N Johnson and Jennifer M Leidy and Christopher L Woodcock and Charles H Robert and Jeffrey C Hansen and Philippe T Georgel} } @article {2009|2009, title = {Structural diversity of the soluble trimers of the human amylin(20-29) peptide revealed by molecular dynamics simulations}, journal = {J. Chem. Phys.}, volume = {130}, number = {12}, year = {2009}, month = {mar}, pages = {125101}, keywords = {Amino Acid Sequence, Amyloid, Humans, Models, Molecular, Molecular Sequence Data, Peptide Fragments, Protein Multimerization, Protein Structure, Quaternary, Solubility, Solvents}, doi = {10.1063/1.3097982}, author = {Mo, Yuxiang and Lu, Yan and Wei, Guanghong and Philippe Derreumaux} } @article {2009|1916, title = {Structures and Thermodynamics of Alzheimer{\textquoteright}s Amyloid-beta A beta(16-35) Monomer and Dimer by Replica Exchange Molecular Dynamics Simulations: Implication for Full-Length A beta Fibrillation}, journal = {J. Phys. Chem. B}, volume = {113}, number = {21}, year = {2009}, month = {may}, pages = {7668{\textendash}7675}, doi = {10.1021/jp900425e}, author = {Y Chebaro and Mousseau, Normand and Philippe Derreumaux} } @article {2009|2019, title = {Thermodynamics and dynamics of amyloid peptide oligomerization are sequence dependent}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {75}, number = {4}, year = {2009}, month = {jun}, pages = {954{\textendash}963}, keywords = {Amino Acid Sequence, Amyloid beta-Protein, beta 2-Microglobulin, Cluster Analysis, Computer Simulation, Models, Molecular, Peptide Fragments, Protein Multimerization, Protein Structure, Secondary, Structure-Activity Relationship, Thermodynamics}, doi = {10.1002/prot.22305}, author = {Lu, Yan and Philippe Derreumaux and Guo, Zhi and Mousseau, Normand and Wei, Guanghong} } @article {2008|1808, title = {Anomalous diffusion of ions at the surface of hydrated DNA molecule}, journal = {Europhys. Lett.}, volume = {82}, year = {2008}, pages = {46002}, author = {Alla Oleinikova and Ivan Brovchenko and Aliaksei Krukau and Alexey K Mazur} } @article {2008|1615, title = {The beta-strand-loop-beta-strand conformation is marginally populated in beta(2)-microglobulin (20-41) peptide in solution as revealed by replica exchange molecular dynamics simulations}, journal = {Biophys. J.}, volume = {95}, number = {2}, year = {2008}, month = {jul}, pages = {510{\textendash}517}, doi = {10.1529/biophysj.107.125054}, author = {Liang, Chungwen and Philippe Derreumaux and Mousseau, Normand and Wei, Guanghong} } @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|1800, title = {The electrostatic origin of low-hydration polymorphism in DNA}, journal = {Chemphyschem in Press}, volume = {9}, year = {2008}, pages = {2691{\textendash}2694}, author = {Alexey K Mazur} } @article {2008|1883, title = {Energy landscapes of the monomer and dimer of the Alzheimer{\textquoteright}s peptide A beta(1-28)}, journal = {J. Chem. Phys.}, volume = {128}, number = {12}, year = {2008}, month = {mar}, pages = {125108}, doi = {10.1063/1.2890033}, author = {Dong, Xiao and Chen, Wei and Mousseau, Normand and Philippe Derreumaux} } @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|1811, title = {Exploring energy landscapes of protein folding and aggregation}, journal = {Front. Biosci.}, volume = {13}, year = {2008}, month = {may}, pages = {4495{\textendash}4516}, doi = {10.2741/3019}, author = {Mousseau, Normand and Philippe Derreumaux} } @article {2008|1451, title = {Fluctuation-induced interactions between dielectrics}, journal = {J. Chem. Phys.}, volume = {129}, year = {2008}, pages = {014703}, author = {S. Pasquali and A.C. Maggs} } @article {2008|1940, title = {HU binds and folds single-stranded DNA}, journal = {Nucl. Acids Res.}, volume = {36}, number = {3}, year = {2008}, pages = {1026{\textendash}1036}, author = {Dmitri Kamashev and Anna Balandina and Alexey K Mazur and Paola B. Arimondo and Josette Rouviere-Yaniv} } @article {2008|1840, title = {Ion dynamics and water percolation effects in DNA polymorphism}, journal = {J. Am. Chem. Soc.}, volume = {130}, number = {1}, year = {2008}, pages = {121{\textendash}131}, author = {Ivan Brovchenko and Aliaksei Krukau and Alla Oleinikova and Alexey K Mazur} } @article {2008|1478, title = {MetaMol: High quality visualization of Molecular Skin Surface}, journal = {J. Mol. Graphics Modell.}, volume = {27}, number = {2}, year = {2008}, pages = {209{\textendash}213}, author = {Matthieu Chavent and B Levy and B Maigret} } @article {2008|1390, title = {Microseconds dynamics simulations of the outer-membrane protease T}, journal = {Biophys. J.}, volume = {94}, number = {1}, year = {2008}, month = {jan}, pages = {71{\textendash}78}, author = {Neri, Marilisa and Marc Baaden and Carnevale, Vincenzo and Anselmi, Claudio and Maritan, Amos and Carloni, Paolo} } @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|1519, title = {Numerical methods for fluctuation driven interactions between dielectrics}, journal = {Phys. Rev. E}, volume = {77}, year = {2008}, pages = {016705}, author = {S. Pasquali and F. Nitti and A.C. Maggs} } @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|1804, title = {Role of the region 23-28 in A beta fibril formation: Insights from simulations of the monomers and dimers of Alzheimer{\textquoteright}s peptides A beta 40 and A beta 42}, journal = {Curr. Alzheimer Res.}, volume = {5}, number = {3}, year = {2008}, month = {jun}, pages = {244{\textendash}250}, doi = {10.2174/156720508784533330}, author = {Melquiond, Adrien and Dong, Xiao and Mousseau, Normand and Philippe Derreumaux} } @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|1862, title = {Statistics of time-limited ensembles of bent DNA conformations}, journal = {J. Phys. Chem. B}, volume = {112}, number = {16}, year = {2008}, pages = {4975{\textendash}4982}, author = {Alexey K Mazur} } @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} } @conference {2008|1552, title = {User Needs Analysis to Design a 3D Multimodal Protein-Docking Interface}, booktitle = {Symposium on 3D User Interfaces 2008 (3DUI 2008 - IEEE)}, year = {2008}, month = {mar}, pages = {125{\textendash}132}, publisher = {Reno - USA}, organization = {Reno - USA}, author = {Nicolas F{\'e}rey and G. Bouyer and C. Martin and P. Bourdot and J. Nelson and and J.M. Burkhardt} } @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|1985, title = {A coarse-grained protein force field for folding and structure prediction}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {69}, number = {2}, year = {2007}, month = {nov}, pages = {394{\textendash}408}, doi = {10.1002/prot.21505}, author = {Maupetit, Julien and Pierre Tuffery and Philippe Derreumaux} } @article {2007|1882, title = {Coarse-grained protein molecular dynamics simulations}, journal = {J. Chem. Phys.}, volume = {126}, number = {2}, year = {2007}, month = {jan}, pages = {025101}, doi = {10.1063/1.2408414}, author = {Philippe Derreumaux and Mousseau, Normand} } @article {2007|2013, title = {Computational Simulations of the Early Steps of Protein Aggregation}, journal = {Prion}, volume = {1}, number = {1}, year = {2007}, month = {jan}, pages = {3{\textendash}8}, author = {Wei, Guanghong and Mousseau, Normand and Philippe Derreumaux} } @article {2007|1776, title = {The conserved glycine/alanine residue of the active-site loop containing the putative acetylCoA-binding motif is essential for the overall structural integrity of Mesorhizobium loti arylamine N-acetyltransferase 1}, journal = {Biochem. Biophys. Res. Commun.}, volume = {361}, number = {1}, year = {2007}, month = {sep}, pages = {256{\textendash}262}, doi = {10.1016/j.bbrc.2007.07.034}, author = {Atmane, Noureddine and Dairou, Julien and Flatters, Delphine and Martins, Marta and Pluvinage, Benjamin and Philippe Derreumaux and Dupret, Jean-Marie and Rodrigues-Lima, Fernando} } @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|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|1954, title = {{P}robing amyloid fibril formation of the {N}{F}{G}{A}{I}{L} peptide by computer simulations}, journal = {J. Chem. Phys.}, volume = {126}, number = {6}, year = {2007}, month = {feb}, pages = {065101}, doi = {10.1063/1.2435358}, author = {Melquiond, A. and Gelly, J.C. and Mousseau, N. and Philippe Derreumaux} } @conference {2007|1491, title = {REVIVOS: REalit{\'e} VIrtuelle pour la construction de VOcabulaires Sp{\'e}cialis{\'e}s}, booktitle = {Journ{\'e}es Francophones d{\textquoteright}Ing{\'e}nierie des Connaissances (AFIA-IC 2007)}, year = {2007}, month = {jul}, address = {Grenoble - France}, author = {Nicolas F{\'e}rey and Claire Toffano-Nioche and Oriane Matte-Taillez and Rachid Gherbi and William Turner} } @article {2007|1881, title = {Sampling small-scale and large-scale conformational changes in proteins and molecular complexes}, journal = {J. Chem. Phys.}, volume = {126}, number = {10}, year = {2007}, month = {mar}, pages = {105101}, doi = {10.1063/1.2710270}, author = {Yun, Mi-Ran and Mousseau, N. and Philippe Derreumaux} } @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 {2007|1861, title = {Water clustering and percolation in low hydration DNA shells}, journal = {J. Phys. Chem. B}, volume = {111}, number = {12}, year = {2007}, pages = {3258{\textendash}3266}, author = {Ivan Brovchenko and Aliaksei Krukau and Alla Oleinikova and Alexey K Mazur} } @article {2007|1949, title = {Wormlike chain theory and bending of short DNA}, journal = {Phys. Rev. Lett.}, volume = {98}, number = {21}, year = {2007}, pages = {218102}, author = {Alexey K Mazur} } @article {2006|1981, title = {Aggregating the amyloid A beta(11-25) peptide into a four-stranded beta-sheet structure}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {65}, number = {4}, year = {2006}, month = {dec}, pages = {877{\textendash}888}, doi = {10.1002/prot.21134}, author = {Boucher, Genevive and Mousseau, Normand and Philippe Derreumaux} } @article {2006|1983, title = {ARTIST: An activated method in internal coordinate space for sampling protein energy landscapes}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {63}, number = {4}, year = {2006}, month = {jun}, pages = {967{\textendash}975}, doi = {10.1002/prot.20938}, author = {Yun, MR and Lavery, R and Mousseau, N and Zakrzewska, K and Philippe Derreumaux} } @article {2006|1843, title = {Comparison of different torsion angle approaches for NMR structure determination}, journal = {J. Biol. Nmr}, volume = {34}, number = {3}, year = {2006}, pages = {153{\textendash}166}, author = {B. Bardiaux and T. E. Malliavin and M. Nilges and Alexey K Mazur} } @article {2006|1880, title = {The conformations of the amyloid-beta (21-30) fragment can be described by three families in solution}, journal = {J. Chem. Phys.}, volume = {125}, number = {8}, year = {2006}, month = {aug}, pages = {084911}, doi = {10.1063/1.2337628}, author = {Chen, Wei and Mousseau, Normand and Philippe Derreumaux} } @article {2006|1388, title = {Evaluation of elastic properties of atomistic DNA models}, journal = {Biophys. J.}, volume = {91}, number = {12}, year = {2006}, pages = {4507{\textendash}4518}, author = {Alexey K Mazur} } @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|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|1810, title = {Normal mode analysis as a prerequisite for drug design: Application to matrix metalloproteinases inhibitors}, journal = {Febs Lett.}, volume = {580}, number = {22}, year = {2006}, month = {oct}, pages = {5130{\textendash}5136}, abstract = {We demonstrate the utility of normal mode analysis in correctly predicting the binding modes of inhibitors in the active sites of matrix metalloproteinases (MMPs). We show the accuracy in predicting the positions of MMP-3 inhibitors is strongly dependent on which structure is used as the target, especially when it has been energy minimized. This dependency can be overcome by using intermediate structures generated along one of the normal modes previously calculated for a given target. These results may be of prime importance for further in silico drug discovery.}, doi = {10.1016/j.febslet.2006.08.037}, author = {Nicolas Floquet and Jean-Didier Mar{\'e}chal and Marie-Ange Badet-Denisot and Charles H Robert and Manuel Dauchez and David Perahia} } @conference {2006, title = {PHYS 4-Applications of activated methods to proteins and materials science}, booktitle = {Abstracts of Papers of the American Chemical Society}, volume = {232}, year = {2006}, author = {Mousseau, Normand and Barkema, Gerard T. and Chubynsky, Mykyta V. and Philippe Derreumaux and El-Mellouhi, Fedwa and Vocks, Henk} } @article {2006|1604, title = {Probing a model of a {GPCR}/ligand complex in an explicit membrane environment: The human cholecystokinin-1 receptor}, journal = {Biophys. J.}, volume = {90}, number = {4}, year = {2006}, pages = {1232{\textendash}1240}, abstract = {A three-dimensional model structure of a complex formed by a G-protein-coupled receptor (GPCR) and an agonist ligand is probed and refined using molecular-dynamics simulations and free energy calculations in a realistic environment. The model of the human receptor of cholecystokinin associated to agonist ligand CCK9 was obtained from a synergistic procedure combining site-directed mutagenesis experiments and in silico modeling. The 31-ns molecular-dynamics simulation in an explicit membrane environment indicates that both the structure of the receptor and its interactions with the ligand are robust. Whereas the secondary structure of the {alpha}-helix bundle is well preserved, the region of the intracellular loops exhibits a significant flexibility likely to be ascribed to the absence of G-protein subunits in the model. New insight into the structural features of the binding pocket is gained, in particular, the interplay of the ligand with both the receptor and internal water molecules. Water-mediated interactions are shown to participate in the binding, hence, suggesting additional site-directed mutagenesis experiments. Accurate free energy calculations on mutated ligands provide differences in the receptor-ligand binding affinity, thus offering a direct, quantitative comparison to experiment. We propose that this detailed consistency-checking procedure be used as a routine refinement step of in vacuo GPCR models, before further investigation and application to structure-based drug design.}, url = {http://www.biophysj.org/cgi/content/abstract/90/4/1232}, author = {J{\'e}r{\^o}me H{\'e}nin and Maigret, B. and Mounir Tarek and Escrieut, C. and Fourmy, D. and Christophe Chipot} } @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 {2006|1982, title = {Structures of soluble amyloid oligomers from computer simulations}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {65}, number = {1}, year = {2006}, month = {oct}, pages = {180{\textendash}191}, doi = {10.1002/prot.21100}, author = {Melquiond, Adrien and Mousseau, Normand and Philippe Derreumaux} } @article {2006|1948, title = {Water percolation governs polymorphic transitions and conductivity of DNA}, journal = {Phys. Rev. Lett.}, volume = {97}, number = {13}, year = {2006}, pages = {137801}, author = {Ivan Brovchenko and Aliaksei Krukau and Alla Oleinikova and Alexey K Mazur} } @conference {2006|1421, title = {Yeast Naked DNA Spatial Organization Predisposes to Transcriptional Regulation}, booktitle = {International Conference on Computational Science and its Applications (ICCSA 2006)}, volume = {3984}, year = {2006}, month = {may}, pages = {222{\textendash}231}, address = {Glasgow, United Kingdom}, author = {O. Matte-Tailliez and J .H{\'e}risson and Nicolas F{\'e}rey and O. Magneau and P.-E. Gros and F. K{\'e}p{\`e}s and R. Gherbi} } @article {2005|1849, title = {Electrostatic polymer condensation and the {A/B} polymorphism in {DNA}: {S}equence effects}, journal = {J. Chem. Theory Comput.}, volume = {1}, year = {2005}, pages = {325{\textendash}336}, author = {Alexey K Mazur} } @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|1378, title = {Exploring the early steps of amyloid peptide aggregation by computers}, journal = {Acc. Chem. Res.}, volume = {38}, number = {11}, year = {2005}, pages = {885{\textendash}891}, author = {Mousseau, N and Philippe Derreumaux} } @article {2005|1879, title = {Following the aggregation of amyloid-forming peptides by computer simulations}, journal = {J. Chem. Phys.}, volume = {122}, number = {17}, year = {2005}, month = {may}, pages = {174904}, doi = {10.1063/1.1886725}, author = {Melquiond, A and Boucher, G and Mousseau, N and Philippe Derreumaux} } @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|1952, title = {Navigation and analysis of the energy landscape of small proteins using the activation-relaxation technique}, journal = {Phys. Biol.}, volume = {2}, number = {4, Sp. Iss. SI}, year = {2005}, month = {dec}, pages = {S101-S107}, doi = {10.1088/1478-3975/2/4/S04}, author = {Mousseau, N and Philippe Derreumaux and Gilbert, G} } @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|1867, title = {The antitumor properties of the alpha 3(IV)-(185-203) peptide from the NC1 domain of type IV collagen (tumstatin) are conformation-dependent}, journal = {J. Biol. Chem.}, volume = {279}, number = {3}, year = {2004}, month = {jan}, pages = {2091{\textendash}2100}, doi = {10.1074/jbc.M307736200}, author = {Floquet, N and Pasco, S and Ramont, L and Philippe Derreumaux and Laronze, JY and Nuzillard, JM and Maquart, FX and Alix, AJP and Monboisse, JC} } @article {2004|1978, title = {Complex folding pathways in a simple beta-hairpin}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {56}, number = {3}, year = {2004}, month = {aug}, pages = {464{\textendash}474}, doi = {10.1002/prot.20127}, author = {Wei, GH and Mousseau, N and Philippe Derreumaux} } @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|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} } @conference {2004|1425, title = {DNA in Virtuo: Visualization and Exploration of 3D Genomic Structures}, booktitle = {International Conference on Virtual Reality, Computer Graphics, Visualization and Interaction (Afrigraph 2005 - ACM-SIGRAPH sponsored)}, year = {2004}, month = {nov}, address = {Stellenbosch (Cap town), South Africa}, author = {J. H{\'e}risson and P.-E. Gros and Nicolas F{\'e}rey and O. Magneau and R. Gherbi} } @conference {2004|1419, title = {DNA in Virtuo: Visualization and Virtual Manipulation of 3D Genomic Structures}, booktitle = {International CODATA Conference, The Information Society: New Horizons for Science}, year = {2004}, month = {nov}, address = {Berlin, Germany}, author = {J. H{\'e}risson and P.-E. Gros and Nicolas F{\'e}rey and O. Magneau and R. Gherbi} } @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|1928, title = {Exploring the early steps of aggregation of amyloid-forming peptide KFFE}, journal = {Journal of Physics-condensed Matter}, volume = {16}, number = {44, Sp. Iss. SI}, year = {2004}, month = {nov}, pages = {S5047-S5054}, doi = {10.1088/0953-8984/16/44/002}, author = {Wei, GH and Mousseau, N and Philippe Derreumaux} } @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|1824, title = {Integrating three views of Arf1 activation dynamics}, journal = {J. Mol. Biol.}, volume = {337}, number = {4}, year = {2004}, month = {apr}, pages = {969{\textendash}983}, author = {Robert, Charles H and Cherfils, Jacqueline and Mouawad, Liliane and Perahia, David} } @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|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|1620, title = {Sampling the self-assembly pathways of KFFE hexamers}, journal = {Biophys. J.}, volume = {87}, number = {6}, year = {2004}, month = {dec}, pages = {3648{\textendash}3656}, doi = {10.1529/biophysj.104.047688}, author = {Wei, G. H. and Mousseau, N. and Philippe Derreumaux} } @article {2004|1778, title = {Single-stranded breaks relax intrinsic curvature in {DNA}?}, journal = {Biochemistry}, volume = {43}, number = {25}, year = {2004}, pages = {8160{\textendash}8168}, author = {Dimitri E. Kamashev and Alexey K Mazur} } @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 {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|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|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|1876, title = {Sampling the complex energy landscape of a simple beta-hairpin}, journal = {J. Chem. Phys.}, volume = {119}, number = {13}, year = {2003}, month = {oct}, pages = {6403{\textendash}6406}, doi = {10.1063/1.1613642}, author = {Wei, GH and Philippe Derreumaux and Mousseau, N} } @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 {2003|1838, title = {Titration {\em in silico} of reversible {B${\l}eftrightarrow$A} transitions in {DNA}}, journal = {J. Am. Chem. Soc.}, volume = {125}, number = {26}, year = {2003}, pages = {7849{\textendash}7859}, author = {Alexey K Mazur} } @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|1946, title = {Comparative bending dynamics in DNA with and without regularly repeated adenine tracts}, journal = {Phys. Rev. E}, volume = {66}, number = {1}, year = {2002}, pages = {011917}, author = {Alexey K Mazur and Dimitri E. Kamashev} } @article {2002|1837, title = {{DNA} dynamics in a water drop without counterions}, journal = {J. Am. Chem. Soc.}, volume = {124}, number = {49}, year = {2002}, pages = {14707{\textendash}14715}, author = {Alexey K Mazur} } @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|1874, title = {Exploring the energy landscape of proteins: A characterization of the activation-relaxation technique}, journal = {J. Chem. Phys.}, volume = {117}, number = {24}, year = {2002}, month = {dec}, pages = {11379{\textendash}11387}, doi = {10.1063/1.1522373}, author = {Wei, GH and Mousseau, N and Philippe Derreumaux} } @article {2002|1599, title = {New insights into the allosteric mechanism of human hemoglobin from molecular dynamics simulations}, journal = {Biophys. J.}, volume = {82}, number = {6}, year = {2002}, month = {jun}, pages = {3224{\textendash}3245}, author = {Mouawad, Liliane and Perahia, David and Charles H. Robert and Guilbert, Christophe} } @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|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, title = {{H}ydration and structural alterations of {A}-{D}{N}{A}. {I}mplications for the accuracy of {D}{N}{A} replication}, journal = {Cell. Mol. Biol. (noisy-le-grand)}, volume = {47}, year = {2001}, pages = {815{\textendash}822}, author = {Mayer, C. and Y Timsit} } @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} } @inbook {2001|1640, title = {Internal coordinate simulation method}, booktitle = {Computational Biochemistry and Biophysics}, year = {2001}, pages = {115{\textendash}131}, publisher = {Marcel Dekker}, organization = {Marcel Dekker}, address = {New York}, author = {Alexey K Mazur}, editor = {Oren M. Becker and Alexander D. MacKerell and Benoit Roux and Masakatsu Watanabe} } @article {2001|1853, title = {Molecular dynamics of minimal B-DNA}, journal = {J. Comput. Chem.}, volume = {22}, number = {4}, year = {2001}, pages = {457{\textendash}467}, author = {Alexey K Mazur} } @article {2001|1844, title = {Molecular dynamics studies of sequence-directed curvature in bending locus of Trypanosome kinetoplast DNA}, journal = {J. Biomol. Struct. Dyn.}, volume = {18}, number = {6}, year = {2001}, pages = {832{\textendash}843}, author = {Alexey K Mazur} } @article {2001|1903, title = {Sampling activated mechanisms in proteins with the activation-relaxation technique}, journal = {Journal of Molecular Graphics \& Modelling}, volume = {19}, number = {1}, year = {2001}, pages = {78{\textendash}86}, doi = {10.1016/S1093-3263(00)00134-0}, author = {Mousseau, N and Philippe Derreumaux and Barkema, GT and Malek, R} } @article {2001|1841, title = {Sheep prion protein synthetic peptide spanning helix 1 and beta-strand 2 (residues 142-166) shows beta-hairpin structure in solution}, journal = {J. Biol. Chem.}, volume = {276}, number = {49}, year = {2001}, pages = {46364{\textendash}46370}, author = {S. A. Kozin and G. Bertho and Alexey K Mazur and H. Rabesona and J. P. Girault and T. Haertle and M. Takahashi and P. Debey and G. H. Hoa} } @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|1490, title = {Cation coordination by calix{[}4]arenes bearing amide and/or phosphine oxide pendant groups: how many arms are needed to bind Li+ vs. Na+? A combined NMR and molecular dynamics study}, journal = {Journal of the Chemical Society-perkin Transactions 2}, number = {7}, year = {2000}, pages = {1315{\textendash}1321}, author = {Marc Baaden and Wipff, G and Yaftian, MR and Burgard, M and Matt, D} } @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} } @inbook {2000|1559, title = {Interfacial features of assisted liquid-liquid extraction of uranyl and cesium salts: a molecular dynamics investigation}, booktitle = {ACS Symposium Series 757}, year = {2000}, pages = {71{\textendash}85}, publisher = {Oxford University Press, New York}, organization = {Oxford University Press, New York}, chapter = {Calixarenes for separations}, author = {Marc Baaden and F. Berny and N. Muzet and L. Troxler and G. Wipff}, editor = {G. Lumetta, R.D. Rogers, and A.S. Gopalan} } @article {2000|1481, title = {M3+ lanthanide cation solvation by acetonitrile: The role of cation size, counterions, and polarization effects investigated by molecular dynamics and quantum mechanical simulations}, journal = {J. Phys. Chem. A}, volume = {104}, number = {32}, year = {2000}, month = {aug}, pages = {7659{\textendash}7671}, author = {Marc Baaden and Berny, F and Madic, C 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 {2000|1836, title = {Theoretical studies of the possible origin of intrinsic static bends in double helical DNA}, journal = {J. Am. Chem. Soc.}, volume = {122}, number = {51}, year = {2000}, pages = {12778{\textendash}12785}, author = {Alexey K Mazur} } @article {1999|1856, title = {Internal correlations in minor groove profiles of experimental and computed B-DNA conformations}, journal = {J. Mol. Biol.}, volume = {290}, year = {1999}, pages = {373{\textendash}377}, author = {Alexey K Mazur} } @article {1999|1845, title = {Symplectic integration of closed chain rigid body dynamics with internal coordinate equations of motion}, journal = {J. Chem. Phys.}, volume = {111}, number = {4}, year = {1999}, pages = {1407{\textendash}1414}, author = {Alexey K Mazur} } @article {1998|1835, title = {Accurate DNA dynamics without accurate long range electrostatics}, journal = {J. Am. Chem. Soc.}, volume = {120}, number = {42}, year = {1998}, pages = {10928{\textendash}10937}, author = {Alexey K Mazur} } @article {1998, title = {{H}ydration and recognition of methylated {C}p{G} steps in {D}{N}{A}}, journal = {Embo J.}, volume = {17}, year = {1998}, month = {may}, pages = {2709{\textendash}2718}, author = {Mayer-Jung, C. and Moras, D. and Y Timsit} } @article {1998|1859, title = {Hierarchy of fast motions in protein dynamics}, journal = {J. Phys. Chem. B}, volume = {102}, number = {2}, year = {1998}, pages = {473{\textendash}479}, author = {Alexey K Mazur} } @article {1997|1854, title = {Common molecular dynamics algorithms revisited: Accuracy and optimal time steps of St{\H o}rmer-leapfrog integrators}, journal = {J. Comput. Phys.}, volume = {136}, number = {2}, year = {1997}, pages = {354{\textendash}365}, author = {Alexey K Mazur} } @article {1997, title = {{E}ffect of cytosine methylation on {D}{N}{A}-{D}{N}{A} recognition at {C}p{G} steps}, journal = {J. Mol. Biol.}, volume = {270}, year = {1997}, month = {jul}, pages = {328{\textendash}335}, author = {Mayer-Jung, C. and Moras, D. and Y Timsit} } @article {1997|1852, title = {Quasi-Hamiltonian equations of motion for internal coordinate molecular dynamics of polymers}, journal = {J. Comput. Chem.}, volume = {18}, number = {11}, year = {1997}, pages = {1354{\textendash}1364}, author = {Alexey K Mazur} } @article {1996, title = {{C}ruciform structures and functions}, journal = {Q. Rev. Biophys.}, volume = {29}, year = {1996}, month = {dec}, pages = {279{\textendash}307}, author = {Y Timsit and Moras, D.} } @article {1996|1660, title = {Molecular modelling study of the netropsin complexation with a nucleic acid triple helix}, journal = {J. Biomol. Struct. Dyn.}, volume = {14}, year = {1996}, month = {dec}, pages = {293{\textendash}302}, abstract = {

A detailed molecular mechanical study has been made on the complexes of netropsin with the double stranded oligonucleotide (dA)12.(dT)12 and with the triple helix (dA)12.(dT)12.(dT)12. The complexes were built using computer graphics and energy refined using JUMNA program. In agreement with circular dichroism experiments we have shown that 3 netropsins can bind the minor grooves of the triple helix and of the double helix. The groove geometry in the duplex and in the triplex is very similar. However a detailed analysis of the energetic terms shows, in agreement with thermal denaturation studies, that the affinity of netropsin toward the double helices is larger than towards triple helices.

}, doi = {10.1080/07391102.1996.10508125}, author = {Vovelle, F and Chantal Pr{\'e}vost and Durand, M and Maurizot, J C} } @article {1995|1632, title = {Investigation of the conformational properties of a {$\beta$}-(1-3) branched {$\beta$}-(1-6) heptasacchardie elicitor and its analogues by internal coordinate stochastic dynamics}, journal = {Carbohydr. Res.}, volume = {279}, year = {1995}, pages = {41{\textendash}57}, author = {Michael G. Petukhov and Alexey K Mazur and Lyudmila A. Elyakova} } @article {1995|1452, title = {{S}elf-fitting and self-modifying properties of the {B}-{D}{N}{A} molecule}, journal = {J. Mol. Biol.}, volume = {251}, year = {1995}, month = {sep}, pages = {629{\textendash}647}, author = {Y Timsit and Moras, D.} } @article {1994|1584, title = {The catalytic mechanism of {$\alpha$}-amylases based upon enzyme crystal structures and model building calculations}, journal = {Biochem. Biophys. Res. Commun.}, volume = {204}, year = {1994}, pages = {297{\textendash}302}, author = {Alexey K Mazur and R. Haser and F. Payan} } @article {1994, title = {{D}{N}{A} self-fitting: the double helix directs the geometry of its supramolecular assembly}, journal = {Embo J.}, volume = {13}, year = {1994}, month = {jun}, pages = {2737{\textendash}2746}, author = {Y Timsit and Moras, D.} } @article {1993|1673, title = {Investigation of conformational equilibrium of polypeptides by internal coordinate stochastic dynamics: Met-enkephalin}, journal = {J. Biomol. Struct. Dyn.}, volume = {10}, year = {1993}, pages = {143{\textendash}167}, author = {Vladimir E. Dorofeyev and Alexey K Mazur} } @article {1993, title = {Multiple attack in the porcine pancreatic alpha-amylase hydrolysis of amylose and amylopectine}, journal = {Arch. Biochem. Biophys.}, volume = {306}, year = {1993}, pages = {29{\textendash}38}, author = {Alexey K Mazur and H. Nakatani} } @article {1993|1682, title = {Optimization of numerical algorithms for internal coordinate molecular dynamics}, journal = {J. Comput. Phys.}, volume = {107}, year = {1993}, pages = {359{\textendash}366}, author = {Vladimir E. Dorofeyev and Alexey K Mazur} } @article {1992, title = {{C}rystallization of {D}{N}{A}}, journal = {Meth. Enzymol.}, volume = {211}, year = {1992}, pages = {409{\textendash}429}, author = {Y Timsit and Moras, D.} } @article {1992|1626, title = {Global optimization of conformation energy of polypeptides by tunnel algorithm}, journal = {Biophysics}, volume = {37}, year = {1992}, pages = {226{\textendash}230}, author = {M. G. Petuhov and V. E. Dorofeyev and R. A. Abagyan and Alexey K Mazur} } @article {1992|1722, title = {Modeling of the possible binding modes of substrates in the active site of {Taka-Amylase A}}, journal = {Mol. Biol.}, volume = {26}, year = {1992}, pages = {292{\textendash}299}, author = {M. G. Petuhov and Alexey K Mazur} } @article {1992|1594, title = {Multiple attack in the mechanism of endoglucanase action}, journal = {Bioorg. Chem.}, volume = {18}, year = {1992}, pages = {1141{\textendash}1163}, author = {P. V. Bezukladnikov and L. A. Elyakova and Alexey K Mazur} } @article {1992|1697, title = {Schematic methods for probabilistic enzyme kinetics}, journal = {J. Theor. Biol.}, volume = {155}, year = {1992}, pages = {387{\textendash}407}, author = {Alexey K Mazur and A. V. Kuchinski} } @article {1991|1503, title = {{B}ase-pairing shift in the major groove of ({C}{A})n tracts by {B}-{D}{N}{A} crystal structures}, journal = {Nature}, volume = {354}, year = {1991}, month = {nov}, pages = {167{\textendash}170}, author = {Y Timsit and Vilbois, E. and Moras, D.} } @article {1991|1683, title = {Derivation and testing of explicit equations of motion for polymers described by internal coordinates}, journal = {J. Comput. Phys.}, volume = {92}, year = {1991}, pages = {261{\textendash}272}, author = {Alexey K Mazur and Vladimir E. Dorofeyev and Ruben A. Abagyan} } @article {1991, title = {{G}roove-backbone interaction in {B}-{D}{N}{A}. {I}mplication for {D}{N}{A} condensation and recombination}, journal = {J. Mol. Biol.}, volume = {221}, year = {1991}, month = {oct}, pages = {919{\textendash}940}, author = {Y Timsit and Moras, D.} } @article {1991|1762, title = {Molecular dynamics of polymers with fixed internal structure: Choice of models and methods}, journal = {Russ. J. Phys. Chem.}, volume = {65}, year = {1991}, pages = {2548{\textendash}2552}, author = {V. E. Dorofeyev and Alexey K Mazur} } @article {1991|1719, title = {NMR and conformational studies of the cyclobutane ring involved in the bicyclo [4.2. 0] octane system of a tetracyclic diterpene structure}, journal = {Magn. Reson. Chem.}, volume = {29}, year = {1991}, pages = {870{\textendash}877}, abstract = {

Conformational studies were performed on the bicyclo [4.2.0] octane system of a series of related tetracyclic diterpenes, using molecular mechanics and 1H NMR. Both methods gave compatible results, but did not permit the deduction of any quantitative relationship linking the vicinal coupling constants to the cyclobutane dihedral angles. Nevertheless, the Karplus relationship allowed a qualitative interpretation of the coupling constants in terms of conformation. A set of characteristic 1H NMR coupling constants was obtained which allows the interpretation of the 1H NMR spectrum of any compound presenting a similar system.

}, doi = {DOI: 10.1002/mrc.1260290903}, url = {http://onlinelibrary.wiley.com/doi/10.1002/mrc.1260290903/full}, author = {Do Khac Manh, Duc and Fetizon, Marcel and Chantal Pr{\'e}vost and Roy, Pierre} } @article {1991|1698, title = {A probabilistic view on steady state enzyme kinetics}, journal = {J. Theor. Biol.}, volume = {148}, year = {1991}, pages = {229{\textendash}242}, author = {Alexey K Mazur} } @article {1990|1638, title = {Conformational energy derivatives for polypeptides with flexible proline rings}, journal = {Comput. \& Chem.}, volume = {14}, year = {1990}, pages = {169{\textendash}175}, author = {Ruben A. Abagyan and Alexey K Mazur} } @article {1990|1723, title = {A new method for analysing of kinetic graphs in enzymatic catalysis}, journal = {Mol. Biol.}, volume = {24}, year = {1990}, pages = {209{\textendash}213}, author = {Alexey K Mazur} } @article {1990|1724, title = {Toward a theory of quasi-steady-state enzymatic processes}, journal = {Mol. Biol.}, volume = {24}, year = {1990}, pages = {202{\textendash}208}, author = {Alexey K Mazur} } @article {1989|1644, title = {A new approach to the modelling of the structure and dynamics of biomacromolecules and their complexes}, journal = {Doklady. Biophysics}, volume = {304}, year = {1989}, pages = {456{\textendash}460}, author = {Alexey K Mazur and R. A. Abagyan and G. B. Elyakov} } @article {1989|1674, title = {New methodology for computer-aided modelling of biomolecular structure and dynamics: 2. Local deformations and cycles}, journal = {J. Biomol. Struct. Dyn.}, volume = {6}, year = {1989}, pages = {833{\textendash}845}, author = {Ruben A. Abagyan and Alexey K Mazur} } @article {1989|1675, title = {New methodology for computer-aided modelling of biomolecular structure and dynamics: 1. Non-cyclic structures}, journal = {J. Biomol. Struct. Dyn.}, volume = {6}, year = {1989}, pages = {815{\textendash}832}, author = {Alexey K Mazur and Ruben A. Abagyan} } @article {1989, title = {{U}nusual helical packing in crystals of {D}{N}{A} bearing a mutation hot spot}, journal = {Nature}, volume = {341}, year = {1989}, month = {oct}, pages = {459{\textendash}462}, author = {Y Timsit and Westhof, E. and Fuchs, R.P. and Moras, D.} } @article {1988|1627, title = {Model of spatial random movement of depolymerase when interacting with the substrate}, journal = {Biophysics}, volume = {23}, year = {1988}, pages = {417{\textendash}421}, author = {Alexey K Mazur and M. G. Petukhov and L. A. Elyakova} } @article {1986, title = {Active sites of the endo-beta-1,3-glucanases from Spisula sacchalinensis and Chlyamys albidys}, journal = {Bioorg. Chem.}, volume = {12}, year = {1986}, pages = {1478{\textendash}1483}, author = {N. I. Nazarova and Alexey K Mazur and L. A. Elyakova} } @article {1986|1652, title = {Ion-Molecule reaction in the gas phase part VI Regioselective SN2 reaction from terpenoid diastereoisomeric diols using CI/NH 4+}, journal = {Helv. Chim. Acta}, volume = {69}, year = {1986}, pages = {806{\textendash}815}, abstract = {

A stereospecific and regioselective SN2 mechanism (Walden inversion) is observed during studies involving modified terpenoid epimeric diols in a high-pressure ion source using ammonia as a reagent gas.

}, doi = {10.1002/hlca.19860690408}, author = {Tabet, Jean-Claude and Chantal Pr{\'e}vost and Bouillot, Anne and Bastard, Josette and Manh, Due Do Khae and Tondeur, Yves} } @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} } @article {1985, title = {Oligomer distribution of depolymerase digests: Comparison of theory and experiments}, journal = {Febs Lett.}, volume = {192}, year = {1985}, pages = {43{\textendash}46}, author = {Alexey K Mazur and N. I. Nazarova and L. A. Elyakova} } @article {1985|1725, title = {On the possible mechanism of multiple enzyme attack in polysaccharide degradation}, journal = {Mol. Biol.}, volume = {19}, year = {1985}, pages = {1400{\textendash}1408}, author = {Alexey K Mazur} } @article {1984, title = {Mathematical models of depolymerization of amylose by alpha-amylases}, journal = {Biopolymers}, volume = {23}, year = {1984}, pages = {1735{\textendash}1756}, author = {Alexey K Mazur} } @article {1984|1629, title = {Most probable distribution at enzyme depolymerization of polysaccharides}, journal = {Biopolymers}, volume = {23}, year = {1984}, pages = {859{\textendash}876}, author = {Alexey K Mazur} } @article {1983, title = {Kinetics of glucose accumulation during depolimerization of polysaccharides by enzymes with different mechanisms of action}, journal = {Mol. Biol.}, volume = {17}, year = {1983}, pages = {101{\textendash}111}, author = {Alexey K Mazur and L. A. Elyakova} } @article {1982, title = {Mathematical modelling of endoglucanase-catalysed hydrolysis of a linear polysaccharide}, journal = {Mol. Biol.}, volume = {16}, year = {1982}, pages = {499{\textendash}510}, author = {L. A. Elyakova and Alexey K Mazur} }