@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|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|2162, title = {Editorial: In Celebration of Women in Science: Biological Modeling and Simulation}, journal = {Front Mol Biosci}, volume = {10}, year = {2023}, pages = {1175325}, author = {Aykac Fas, B and S Sacquin-Mora and Papaleo, E} } @article {2023|2166, title = {It Takes Tau to Tango: Investigating the Fuzzy Interaction between the R2-Repeat Domain and Tubulin C-Terminal Tails}, journal = {Biochemistry}, volume = {62}, year = {2023}, month = {Aug}, pages = {2492{\textendash}2502}, author = {Marien, J and Prevost, C and S Sacquin-Mora} } @article {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|2157, title = {Consistent Picture of Phosphate{\textendash}Divalent Cation Binding from Models with Implicit and Explicit Electronic Polarization}, journal = {J. Phys. Chem. B}, volume = {126}, year = {2022}, month = {05/2022}, pages = {4022-4034}, doi = {10.1021/acs.jpcb.2c01158}, url = {https://pubs.acs.org/doi/full/10.1021/acs.jpcb.2c01158}, author = {Julie Puyo-Fourtine and Marie Juill{\'e} and J{\'e}r{\^o}me H{\'e}nin and Carine Clavagu{\'e}ra and Elise Dubou{\'e}-Dijon} } @article {2022|2150, title = {Modeling the Dynamics of Protein-Protein Interfaces, How and Why?}, journal = {Molecules}, volume = {27}, year = {2022}, pages = {1841}, abstract = {

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

}, issn = {1420-3049}, doi = {10.3390/molecules27061841}, url = {https://www.mdpi.com/1420-3049/27/6/1841}, author = {Karaca, Ezgi and Pr{\'e}vost, Chantal and S Sacquin-Mora} } @article {2022|2160, title = {Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation}, journal = {Nature Communications}, volume = {13}, year = {2022}, doi = {10.1038/s41467-022-34813-5}, url = {https://doi.org/10.1038/s41467-022-34813-5}, author = {John T. Petroff and Noah M. Dietzen and Ezry Santiago-McRae and Brett Deng and Maya S. Washington and Lawrence J. Chen and K. Trent Moreland and Zengqin Deng and Michael Rau and James A. J. Fitzpatrick and Peng Yuan and Thomas T. Joseph and J{\'e}r{\^o}me H{\'e}nin and Grace Brannigan and Wayland W. L. Cheng} } @article {2021|2154, title = {Influences of ssDNA-RecA Filament Length on the Fidelity of Homologous Recombination}, journal = {Journal of Molecular Biology}, volume = {433}, year = {2021}, pages = {167143}, abstract = {

Chromosomal double-strand breaks can be accurately repaired by homologous recombination, but genomic rearrangement can result if the repair joins different copies of a repeated sequence. Rearrangement can be advantageous or fatal. During repair, a broken double-stranded DNA (dsDNA) is digested by the RecBCD complex from the 5 {\"A} end, leaving a sequence gap that separates two 3{\"A} single-stranded DNA (ssDNA) tails. RecA binds to the 3 {\"A} tails forming helical nucleoprotein filaments.A three-strand intermediate is formed when a RecA-bound ssDNA with L nucleotides invades a homologous region of dsDNA and forms a heteroduplex product with a length \≤ L bp. The homology dependent stability of the heteroduplex determines how rapidly and accurately homologous recombination repairs double-strand breaks. If the heteroduplex is sufficiently sequence matched, repair progresses to irreversible DNA synthesis. Otherwise, the heteroduplex should rapidly reverse. In this work, we present in vitro measurements of the L dependent stability of heteroduplex products formed by filaments with 90 \≤ L \≤ 420 nt, which is within the range observed in vivo. We find that without ATP hydrolysis, products are irreversible when L \> 50 nt. In contrast, with ATP hydrolysis when L \< 160 nt, products reverse in \< 30 seconds; however, with ATP hydrolysis when L \>= 320 nt, some products reverse in \< 30 seconds, while others last thousands of seconds. We consider why these two different filament length regimes show such distinct behaviors. We propose that the experimental results combined with theoretical insights suggest that filaments with 250 \≤ L \≤ 8500 nt optimize DSB repair.

}, keywords = {biased random walk, D-loop turnover, Double-strand break repair, genomic rearrangement, multiple reversible intermediates}, issn = {0022-2836}, doi = {https://doi.org/10.1016/j.jmb.2021.167143}, url = {https://www.sciencedirect.com/science/article/pii/S0022283621003727}, author = {Claudia Danilowicz and Evan Vietorisz and Veronica Godoy-Carter and Chantal Pr{\'e}vost and Mara Prentiss} } @article {2021|2155, title = {Modeling Perturbations in Protein Filaments at the Micro and Meso Scale Using NAMD and PTools/Heligeom}, journal = {Bio-protocol}, volume = {11}, year = {2021}, pages = {e4097}, abstract = {

Protein filaments are dynamic entities that respond to external stimuli by slightly or substantially modifying the internal binding geometries between successive protomers. This results in overall changes in the filament architecture, which are difficult to model due to the helical character of the system. Here, we describe how distortions in RecA nucleofilaments and their consequences on the filament-DNA and bound DNA-DNA interactions at different stages of the homologous recombination process can be modeled using the PTools/Heligeom software and subsequent molecular dynamics simulation with NAMD. Modeling methods dealing with helical macromolecular objects typically rely on symmetric assemblies and take advantage of known symmetry descriptors. Other methods dealing with single objects, such as MMTK or VMD, do not integrate the specificities of regular assemblies. By basing the model building on binding geometries at the protomer-protomer level, PTools/Heligeom frees the building process from a priori knowledge of the system topology and enables irregular architectures and symmetry disruption to be accounted for. doi: 10.21769/BioProtoc.4097

}, doi = {10.21769/BioProtoc.4097}, url = {www.bioprotocol.org/e4097}, author = {Boyer, B. and Laurent, B. and Robert, C. H. and Prevost, C.} } @article {2021, title = {Moving pictures: Reassessing docking experiments with a dynamic view of protein interfaces.}, journal = {Proteins}, year = {2021}, month = {2021 May 26}, abstract = {

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

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

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

}, issn = {2218-273X}, doi = {10.3390/biom11101529}, url = {https://www.mdpi.com/2218-273X/11/10/1529}, author = {S Sacquin-Mora and Chantal Pr{\'e}vost} } @article {2020|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|2142, title = {Scalable molecular dynamics on CPU and GPU architectures with NAMD}, journal = {The Journal of Chemical Physics}, volume = {153}, year = {2020}, chapter = {044130}, abstract = {

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

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

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

}, doi = {10.1093/nar/gkz1071}, author = {R{\"o}der, Konstantin and Guillaume Stirnemann and Dock-Bregeon, Anne-Catherine and Wales, David J and Pasquali, Samuela} } @article {2019|2060, title = {Conformational Stability Adaptation of a Double-Stranded RNA-Binding Domain to Transfer RNA Ligand.}, journal = {Biochemistry}, volume = {58}, year = {2019}, month = {2019 May 21}, pages = {2463-2473}, abstract = {

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

}, issn = {1520-4995}, doi = {10.1021/acs.biochem.9b00111}, author = {Bou-Nader, Charles and Pecqueur, Ludovic and Barraud, Pierre and Fontecave, Marc and Tisn{\'e}, Carine and S Sacquin-Mora and Hamdane, Djemel} } @article {2019|2067, title = {An inter-dimer allosteric switch controls NMDA receptor activity}, journal = {The EMBO journal}, volume = {38}, year = {2019}, author = {Esmenjaud, Jean-Baptiste and Stroebel, David and Chan, Kelvin and Grand, Teddy and David, M{\'e}lissa and Wollmuth, Lonnie P and Antoine Taly and Paoletti, Pierre} } @article {2019|2068, title = {Molecular modelling as the spark for active learning approaches for interdisciplinary biology teaching}, journal = {Interface focus}, volume = {9}, year = {2019}, pages = {20180065}, author = {Antoine Taly and Nitti, Francesco and Marc Baaden and Pasquali, S} } @article {2019|2062, title = {The positioning of Chi sites allows the RecBCD pathway to suppress some genomic rearrangements}, journal = {Nucleic Acids Res}, volume = {47}, year = {2019}, month = {02}, pages = {1836-1846}, abstract = {

Bacterial recombinational repair of double-strand breaks often begins with creation of initiating 3\&$\#$39; single-stranded DNA (ssDNA) tails on each side of a double-strand break (DSB). Importantly, if the RecBCD pathway is followed, RecBCD creates a gap between the sequences at 3\&$\#$39; ends of the initiating strands. The gap flanks the DSB and extends at least to the nearest Chi site on each strand. Once the initiating strands form ssDNA-RecA filaments, each ssDNA-RecA filament searches for homologous double-stranded DNA (dsDNA) to use as a template for the DNA synthesis needed to fill the gap created by RecBCD. Our experimental results show that the DNA synthesis requires formation of a heteroduplex dsDNA that pairs \>20 contiguous bases in the initiating strand with sequence matched bases in a strand from the original dsDNA. To trigger synthesis, the heteroduplex must be near the 3\&$\#$39; end of the initiating strand. Those experimentally determined requirements for synthesis combined with the Chi site dependence of the function of RecBCD and the distribution of Chi sites in bacterial genomes could allow the RecBCD pathway to avoid some genomic rearrangements arising from directly induced DSBs; however, the same three factors could promote other rearrangements.

}, doi = {10.1093/nar/gky1252}, author = {Li, Chastity and Danilowicz, Claudia and Tashjian, Tommy F and Godoy, Veronica G and Chantal Pr{\'e}vost and Prentiss, Mara} } @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|2064, title = {Slow extension of the invading DNA strand in a D-loop formed by RecA-mediated homologous recombination may enhance recognition of DNA homology}, journal = {J Biol Chem}, volume = {294}, year = {2019}, month = {May}, pages = {8606-8616}, abstract = {

DNA recombination resulting from RecA-mediated strand exchange aided by RecBCD proteins often enables accurate repair of DNA double-strand breaks. However, the process of recombinational repair between short DNA regions of accidental similarity can lead to fatal genomic rearrangements. Previous studies have probed how effectively RecA discriminates against interactions involving a short similar sequence that is embedded in otherwise dissimilar sequences but have not yielded fully conclusive results. Here, we present results of in vitro experiments with fluorescent probes strategically located on the interacting DNA fragments used for recombination. Our findings suggest that DNA synthesis increases the stability of the recombination products. Fluorescence measurements can also probe the homology dependence of the extension of invading DNA strands in D-loops formed by RecA-mediated strand exchange. We examined the slow extension of the invading strand in a D-loop by DNA polymerase (Pol) IV and the more rapid extension by DNA polymerase LF-Bsu We found that when DNA Pol IV extends the invading strand in a D-loop formed by RecA-mediated strand exchange, the extension afforded by 82 bp of homology is significantly longer than the extension on 50 bp of homology. In contrast, the extension of the invading strand in D-loops by DNA LF-Bsu Pol is similar for intermediates with \≥50 bp of homology. These results suggest that fatal genomic rearrangements due to the recombination of small regions of accidental homology may be reduced if RecA-mediated strand exchange is immediately followed by DNA synthesis by a slow polymerase.

}, keywords = {cooperativity, DNA damage, DNA polymerase, DNA recombination, double-strand break (DSB), fluorescence resonance energy transfer (FRET), heteroduplex formation, molecular dynamics, RecA, strand displacement synthesis}, doi = {10.1074/jbc.RA119.007554}, author = {Lu, Daniel and Danilowicz, Claudia and Tashjian, Tommy F and Chantal Pr{\'e}vost and Godoy, Veronica G and Prentiss, Mara} } @article {2019|2065, title = {Weaving DNA strands: structural insight on ATP hydrolysis in RecA-induced homologous recombination}, journal = {Nucleic Acids Res}, volume = {47}, year = {2019}, month = {Sep}, pages = {7798-7808}, abstract = {

Homologous recombination is a fundamental process in all living organisms that allows the faithful repair of DNA double strand breaks, through the exchange of DNA strands between homologous regions of the genome. Results of three decades of investigation and recent fruitful observations have unveiled key elements of the reaction mechanism, which proceeds along nucleofilaments of recombinase proteins of the RecA family. Yet, one essential aspect of homologous recombination has largely been overlooked when deciphering the mechanism: while ATP is hydrolyzed in large quantity during the process, how exactly hydrolysis influences the DNA strand exchange reaction at the structural level remains to be elucidated. In this study, we build on a previous geometrical approach that studied the RecA filament variability without bound DNA to examine the putative implication of ATP hydrolysis on the structure, position, and interactions of up to three DNA strands within the RecA nucleofilament. Simulation results on modeled intermediates in the ATP cycle bring important clues about how local distortions in the DNA strand geometries resulting from ATP hydrolysis can aid sequence recognition by promoting local melting of already formed DNA heteroduplex and transient reverse strand exchange in a weaving type of mechanism.

}, doi = {10.1093/nar/gkz667}, author = {Boyer, Benjamin and Danilowicz, Claudia and Prentiss, Mara and Chantal Pr{\'e}vost} } @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|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|2132, title = {The force-dependent mechanism of DnaK-mediated mechanical folding}, journal = {Sci Adv}, volume = {4}, year = {2018}, month = {Feb}, pages = {eaaq0243}, abstract = {

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

}, doi = {10.1126/sciadv.aaq0243}, author = {Perales-Calvo, Judit and Giganti, David and Guillaume Stirnemann and Garcia-Manyes, Sergi} } @article {2018|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|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, 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} } @booklet {2018|2066, title = {Ten simple rules to create a serious game, illustrated with examples from structural biology}, year = {2018}, author = {Marc Baaden and Delalande, Olivier and Nicolas F{\'e}rey and Pasquali, Samuela and Waldisp{\"u}hl, J{\'e}r{\^o}me and Antoine Taly} } @article {2017|2022, title = {ATP hydrolysis provides functions that promote rejection of pairings between different copies of long repeated sequences}, journal = {Nucleic Acids Res}, volume = {45}, year = {2017}, pages = {8448-8462}, abstract = {

During DNA recombination and repair, RecA family proteins must promote rapid joining of homologous DNA. Repeated sequences with \>100 base pair lengths occupy more than 1\% of bacterial genomes; however, commitment to strand exchange was believed to occur after testing ~20-30 bp. If that were true, pairings between different copies of long repeated sequences would usually become irreversible. Our experiments reveal that in the presence of ATP hydrolysis even 75 bp sequence-matched strand exchange products remain quite reversible. Experiments also indicate that when ATP hydrolysis is present, flanking heterologous dsDNA regions increase the reversibility of sequence matched strand exchange products with lengths up to ~75 bp. Results of molecular dynamics simulations provide insight into how ATP hydrolysis destabilizes strand exchange products. These results inspired a model that shows how pairings between long repeated sequences could be efficiently rejected even though most homologous pairings form irreversible products.

}, doi = {10.1093/nar/gkx582}, author = {Danilowicz, Claudia and Hermans, Laura and Coljee, Vincent and Chantal Pr{\'e}vost and Prentiss, Mara} } @article {2017|2033, title = {Configurational Disorder of Water Hydrogen Bond Network at the Protein Dynamical Transition}, volume = {121}, year = {2017}, pages = {6792-6798}, author = {O. Rahaman and M. Kalimeri and M. Katava and A. Paciaroni and F. Sterpone} } @article {2017|2025, title = {Critical structural fluctuations of proteins upon thermal unfolding challenge the Lindemann criterion}, journal = {Proc Natl Acad Sci U S A}, volume = {114}, year = {2017}, month = {Aug}, pages = {9361-9366}, abstract = {

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

}, keywords = {cell thermal stability, Lindemann criterion, Molecular Dynamics Simulation, neutron scattering, protein dynamics}, doi = {10.1073/pnas.1707357114}, author = {Katava, Marina and Guillaume Stirnemann and Zanatta, Marco and Capaccioli, Simone and Pachetti, Maria and Ngai, K L and Sterpone, Fabio and Paciaroni, Alessandro} } @article {2017|2020, title = {Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {May}, pages = {1858}, author = {Colloc{\textquoteright}h, N. and S Sacquin-Mora and Avella, G. and Dhaussy, A. C. and Prange, T. and Vallone, B. and Girard, E.} } @article {2017|2041, title = {Fast coarse-grained model for RNA titration.}, journal = {J Chem Phys}, volume = {146}, year = {2017}, month = {2017 Jan 21}, pages = {035101}, abstract = {

A new numerical scheme for RNA (ribonucleic acid) titration based on the Debye-H{\"u}ckel framework for the salt description is proposed in an effort to reduce the computational costs for further applications to study protein-RNA systems. By means of different sets of Monte Carlo simulations, we demonstrated that this new scheme is able to correctly reproduce the experimental titration behavior and salt pKshifts. In comparison with other theoretical approaches, similar or even better outcomes are achieved at much lower computational costs. The model was tested on the lead-dependent ribozyme, the branch-point helix, and the domain 5 from Azotobacter vinelandii Intron 5.

}, keywords = {Azotobacter vinelandii, Introns, Models, Chemical, Molecular Dynamics Simulation, Monte Carlo Method, Protein Structure, Secondary, Protons, RNA, RNA, Catalytic, Titrimetry}, issn = {1089-7690}, doi = {10.1063/1.4972986}, author = {Barroso da Silva, Fernando Luis and Philippe Derreumaux and Pasquali, Samuela} } @article {2017, title = {Mobility and core-protein binding patterns of disordered C-terminal tails in β-tubulin isotypes.}, journal = {Biochemistry}, volume = { 56}, year = {2017}, pages = {1746{\textendash}1756}, chapter = {1746}, abstract = {

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

}, doi = {10.1021/acs.biochem.6b00988}, author = {Laurin, Yoann and Eyer, Joel and Charles H. Robert and Chantal Pr{\'e}vost and S Sacquin-Mora} } @article {2017|2037, title = {Multifunctional energy landscape for a DNA G-quadruplex: An evolved molecular switch.}, journal = {J Chem Phys}, volume = {147}, year = {2017}, month = {2017 Oct 21}, pages = {152715}, abstract = {

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

}, issn = {1089-7690}, doi = {10.1063/1.4997377}, author = {Cragnolini, Tristan and Chakraborty, Debayan and Sponer, Jiri and Philippe Derreumaux and Pasquali, Samuela and Wales, David J} } @article {2017|2038, title = {Protein-RNA complexation driven by the charge regulation mechanism.}, journal = {Biochem Biophys Res Commun}, year = {2017}, month = {2017 Jul 12}, abstract = {

Electrostatic interactions play a pivotal role in many (bio)molecular association processes. The molecular organization and function in biological systems are largely determined by these interactions from pure Coulombic contributions to more peculiar mesoscopic forces due to ion-ion correlation and proton fluctuations. The latter is a general electrostatic mechanism that gives attraction particularly at low electrolyte concentrations. This charge regulation mechanism due to titrating amino acid and nucleotides residues is discussed here in a purely electrostatic framework. By means of constant-pH Monte Carlo simulations based on a fast coarse-grained titration proton scheme, a new computer molecular model was devised to study protein-RNA interactions. The complexation between the RNA silencing suppressor p19 viral protein and the 19-bp small interfering RNA was investigated at different solution pH and salt conditions. The outcomes illustrate the importance of the charge regulation mechanism that enhances the association between these macromolecules in a similar way as observed for other protein-polyelectrolyte systems typically found in colloidal science. Due to the highly negative charge of RNA, the effect is more pronounced in this system as predicted by the Kirkwood-Shumaker theory. Our results contribute to the general physico-chemical understanding of macromolecular complexation and shed light on the extensive role of RNA in the cell\&$\#$39;s life.

}, issn = {1090-2104}, doi = {10.1016/j.bbrc.2017.07.027}, author = {Barroso da Silva, Fernando Luis and Philippe Derreumaux and Pasquali, Samuela} } @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|2102, title = {Visualization of Biomolecular Structures: State of the Art Revisited: Visualization of Biomolecular Structures}, journal = {Computer Graphics Forum}, volume = {36}, year = {2017}, pages = {178{\textendash}204}, issn = {01677055}, doi = {10.1111/cgf.13072}, url = {http://doi.wiley.com/10.1111/cgf.13072}, author = {Kozlikova, B. and Krone, M. and Falk, M. and Lindow, N. and Marc Baaden and Baum, D. and Viola, I. and Parulek, J. and Hege, H.-C.} } @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|1707, title = {Coarse-Grained Simulations Complemented by Atomistic Molecular Dynamics Provide New Insights into Folding and Unfolding of Human Telomeric G-Quadruplexes}, journal = {J. Chem. Theory Comput.}, volume = {12}, number = {12}, year = {2016}, month = {dec}, pages = {6077{\textendash}6097}, abstract = {G-quadruplexes are the most important non canonical DNA architectures. Many quadruplex-forming sequences, including the human telomeric sequence d(GGGTTA)(n), have been investigated due to their implications in cancer and other diseases, and because of their potential in DNA-based nanotechnology. Despite the availability of atomistic structural studies of folded G-quadruplexes, their folding pathways remain mysterious, and mutually contradictory models of folding coexist in the literature. Recent experiments convincingly demonstrated that G-quadruplex folding often takes days to reach thermodynamic equilibrium. Based on atomistic simulations of diverse classes of intermediates in G-quadruplex folding, we have suggested that the folding is an extremely multipathway process combining a kinetic partitioning mechanism with conformational diffusion. However, complete G-quadruplex folding is far beyond the time scale of atomistic simulations. Here we use high-resolution coarse-grained simulations to investigate potential unfolding intermediates, whose structural dynamics are then further explored with all-atom simulations. This multiscale approach indicates how various pathways are interconnected in a complex network. Spontaneous conversions between different folds are observed. We demonstrate the inability of simple order parameters, such as radius of gyration or the number of native H-bonds, to describe the folding landscape of the G-quadruplexes. Our study also provides information relevant to further development of the coarse grained force field.}, issn = {1549-9618}, doi = {10.1021/acs.jctc.6b00667}, author = {Stadlbauer, Petr and Mazzanti, Liuba and Cragnolini, Tristan and Wales, David J. and Philippe Derreumaux and Pasquali, Samuela and Sponer, Jiri} } @article {2016|1712, title = {Dimerization Mechanism of Alzheimer A beta(40) Peptides: The High Content of Intrapeptide-Stabilized Conformations in A2V and A2T Heterozygous Dimers Retards Amyloid Fibril Formation}, journal = {J. Phys. Chem. B}, volume = {120}, number = {47}, year = {2016}, pages = {12111{\textendash}12126}, abstract = {Amyloid beta (A beta) oligomerization is associated with the origin and progression of Alzheimer{\textquoteright}s disease (AD). While the A2V mutation enhances aggregation kinetics and toxicity, mixtures of wild-type (WT) and A2V, and also WT and A2T, peptides retard fibril formation and protect against AD. In this study, we simulate the equilibrium ensemble of WT:A2T A beta(40) dimer by means of extensive atomistic replica exchange molecular dynamics and compare our results with previous equivalent simulations of A2V:A2V, WT:WT, and WT:A2V A beta(40) dimers for a total time scale of nearly 0.1 ms. Qualitative comparison of the resulting thermodynamic properties, such as the relative binding free energies, with the reported experimental kinetic and thermodynamic data affords us important insight into the conversion from slow-pathway to fast-pathway dimer conformations. The crucial reaction coordinate or driving force of such transformation turns out to be related to hydrophobic interpeptide interactions. Analysis of the equilibrium ensembles shows that the fast-pathway conformations contain interpeptide out-of-register antiparallel beta-sheet structures at short interpeptide distances. In contrast, the slow-pathway conformations are formed by the association of peptides at large interpeptide distances and high intrapeptide compactness, such as conformations containing intramolecular three-stranded beta-sheets which sharply distinguish fast (A2V:A2V and WT:WT) and slow (WT:A2T and WT:A2V) amyloid-forming sequences. Also, this analysis leads us to predict that a molecule stabilizing the intramolecular three-stranded beta-sheet or inhibiting the formation of an interpeptide beta-sheet spanning residues 17-20 and 31-37 would further reduce fibril formation and probably the cytotoxicity of A beta species.}, issn = {1520-6106}, doi = {10.1021/acs.jpcp.6b10722}, author = {Phuong Hoang Nguyen and Fabio Sterpone and Pouplana, Ramon and Philippe Derreumaux and Campanera, Josep M.} } @article {2016|1765, title = {Electrostatics analysis of the mutational and pH effects of the N-terminal domain self-association of the major ampullate spidroin}, journal = {Soft Matter}, volume = {12}, number = {25}, year = {2016}, pages = {5600{\textendash}5612}, abstract = {Spider silk is a fascinating material combining mechanical properties such as maximum strength and high toughness comparable or better than man-made materials, with biocompatible degradability characteristics. Experimental measurements have shown that pH triggers the dimer formation of the N-terminal domain (NTD) of the major ampullate spidroin 1 (MaSp 1). A coarse-grained model accounting for electrostatics, van der Waals and pH-dependent charge-fluctuation interactions, by means of Monte Carlo simulations, gave us a more comprehensive view of the NTD dimerization process. A detailed analysis of the electrostatic properties and free energy derivatives for the NTD homoassociation was carried out at different pH values and salt concentrations for the protein wild type and for several mutants. We observed an enhancement of dipole-dipole interactions at pH 6 due to the ionization of key amino acids, a process identified as the main driving force for dimerization. Analytical estimates based on the DVLO theory framework corroborate our findings. Molecular dynamics simulations using the OPEP coarse-grained force field for proteins show that the mutant E17Q is subject to larger structural fluctuations when compared to the wild type. Estimates of the association rate constants for this mutant were evaluated by the Debye-Smoluchowski theory and are in agreement with the experimental data when thermally relaxed structures are used instead of the crystallographic data. Our results can contribute to the design of new mutants with specific association properties.}, issn = {1744-683X}, doi = {10.1039/c6sm00860g}, author = {Barroso da Silva, Fernando Luis and Pasquali, Samuela and Philippe Derreumaux and Dias, Luis Gustavo} } @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|1763, title = {Structure of ring-shaped Aβ42 oligomers determined by conformational selection}, journal = {Sci. Rep.}, volume = {6}, year = {2016}, pages = {21429}, abstract = {

The oligomerization of amyloid beta (Aβ) peptides into soluble non-fibrillar species plays a critical role in the pathogenesis of Alzheimer\&$\#$39;s disease. However, it has been challenging to characterize the tertiary and quaternary structures of Aβ peptides due to their disordered nature and high aggregation propensity. In this work, replica exchange molecular dynamics simulations were used to explore the conformational space of Aβ42 monomer. Among the most populated transient states, we identified a particular conformation which was able to generate ring-shaped pentamers and hexamers, when docked onto itself. The structures of these aggregates were stable during microsecond all-atom MD simulations in explicit solvent. In addition to high resolution models of these oligomers, this study provides support for the conformational selection mechanism of Aβ peptide self-assembly.

}, issn = {2045-2322}, doi = {10.1038/srep21429}, author = {Tran, Linh and Basdevant, Nathalie and Chantal Pr{\'e}vost and Ha-Duong, T{\^a}p} } @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} } @article {2016, title = {Visual Analysis of Biomolecular Cavities: State of the Art}, journal = {Comput. Graphics Forum}, volume = {35}, number = {3}, year = {2016}, month = {jun}, pages = {527{\textendash}551}, keywords = {AMBIENT OCCLUSION, ANALYTICAL SHAPE, BINDING-SITE IDENTIFICATION, LIGAND-BINDING, PORE DIMENSIONS, PROTEIN CAVITIES, SURFACE, TIME MOLECULAR VISUALIZATION, TRAVEL DEPTH, WEB SERVER}, url = {https://hal.archives-ouvertes.fr/hal-01400464}, author = {Krone, M. and Kozlikova, B. and Lindow, N. and Marc Baaden and Baum, D. and Parulek, J. and Hege, H.-C. and Viola, I.} } @article {2016|1401, title = {Visualization of Biomolecular Structures: State of the Art Revisited}, journal = {Comput. Graphics Forum}, year = {2016}, month = {nov}, url = {https://hal.archives-ouvertes.fr/hal-01400465}, author = {Kozlikova, B. and Krone, M. and Falk, M. and Lindow, N. and Marc Baaden and Baum, D. and Viola, I. and Parulek, J. and Hege, H.-C.} } @article {2016|1633, title = {Water Determines the Structure and Dynamics of Proteins}, journal = {Chem. Rev.}, volume = {116}, year = {2016}, pages = {7673{\textendash}7697}, author = {M-C. Bellissent-Funel and A. Hassanali and M. Havenith and R. Henchman and P. Pohl and Fabio Sterpone and D. van der Spoel and Y. Xu and A. E. Garcia} } @article {2015|1716, title = {Ab initio RNA folding}, journal = {Journal of Physics-condensed Matter}, volume = {27}, number = {23}, year = {2015}, month = {jun}, pages = {233102}, doi = {10.1088/0953-8984/27/23/233102}, author = {Cragnolini, Tristan and Philippe Derreumaux and Pasquali, Samuela} } @article {2015|1667, title = {The adaptive biasing force method: everything you always wanted to know but were afraid to ask.}, journal = {J. Phys. Chem. B}, volume = {119}, year = {2015}, month = {jan}, pages = {1129{\textendash}51}, abstract = {

In the host of numerical schemes devised to calculate free energy differences by way of geometric transformations, the adaptive biasing force algorithm has emerged as a promising route to map complex free-energy landscapes. It relies upon the simple concept that as a simulation progresses, a continuously updated biasing force is added to the equations of motion, such that in the long-time limit it yields a Hamiltonian devoid of an average force acting along the transition coordinate of interest. This means that sampling proceeds uniformly on a flat free-energy surface, thus providing reliable free-energy estimates. Much of the appeal of the algorithm to the practitioner is in its physically intuitive underlying ideas and the absence of any requirements for prior knowledge about free-energy landscapes. Since its inception in 2001, the adaptive biasing force scheme has been the subject of considerable attention, from in-depth mathematical analysis of convergence properties to novel developments and extensions. The method has also been successfully applied to many challenging problems in chemistry and biology. In this contribution, the method is presented in a comprehensive, self-contained fashion, discussing with a critical eye its properties, applicability, and inherent limitations, as well as introducing novel extensions. Through free-energy calculations of prototypical molecular systems, many methodological aspects are examined, from stratification strategies to overcoming the so-called hidden barriers in orthogonal space, relevant not only to the adaptive biasing force algorithm but also to other importance-sampling schemes. On the basis of the discussions in this paper, a number of good practices for improving the efficiency and reliability of the computed free-energy differences are proposed.

}, issn = {1520-5207}, doi = {10.1021/jp506633n}, author = {Comer, Jeffrey and Gumbart, James C and J{\'e}r{\^o}me H{\'e}nin and Leli{\`e}vre, Tony and Pohorille, Andrew and Christophe Chipot} } @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|1708, title = {Coarse-Grained HiRE-RNA Model for ab Initio RNA Folding beyond Simple Molecules, Including Noncanonical and Multiple Base Pairings}, journal = {J. Chem. Theory Comput.}, volume = {11}, number = {7}, year = {2015}, pages = {3510{\textendash}3522}, doi = {10.1021/acs.jctc.5b00200}, author = {Cragnolini, Tristan and Laurin, Yoann and Philippe Derreumaux and Pasquali, Samuela} } @article {2015|1766, title = {Docking Peptides on Proteins: How to Open a Lock, in the Dark, with a Flexible Key}, journal = {Structure}, volume = {23}, number = {8}, year = {2015}, month = {aug}, pages = {1373{\textendash}1374}, doi = {10.1016/j.str.2015.07.004}, author = {S Sacquin-Mora and Chantal Pr{\'e}vost} } @article {2015|1780, title = {{E}pock: rapid analysis of protein pocket dynamics}, journal = {Bioinformatics}, volume = {31}, number = {9}, year = {2015}, month = {may}, pages = {1478{\textendash}1480}, doi = {10.1093/bioinformatics/btu822}, author = {Laurent, Benoist and Matthieu Chavent and Cragnolini, Tristan and Dahl, Anna Caroline E. and Pasquali, Samuela and Philippe Derreumaux and Sansom, Mark S. P. and Marc Baaden} } @article {2015|1582, title = {The elastic free energy of a tandem modular protein under force.}, journal = {Biochem. Biophys. Res. Comm.}, year = {2015}, pages = {1{\textendash}5}, keywords = {free energy landscape, tandem modular protein}, issn = {0006291X}, doi = {10.1016/j.bbrc.2015.03.051}, url = {http://linkinghub.elsevier.com/retrieve/pii/S0006291X15004866}, author = {Valle-Orero, Jessica and Eckels, Edward and Guillaume Stirnemann and Popa, Ionel and Berkovich, Ronen and Fernandez, Julio M.} } @article {2015|1731, title = {Integrating multi-scale data on homologous recombination into a new recognition mechanism based on simulations of the RecA-ssDNA/dsDNA structure}, journal = {Nucleic Acids Res.}, volume = {43}, year = {2015}, month = {dec}, pages = {10251{\textendash}63}, abstract = {

RecA protein is the prototypical recombinase. Members of the recombinase family can accurately repair double strand breaks in DNA. They also provide crucial links between pairs of sister chromatids in eukaryotic meiosis. A very broad outline of how these proteins align homologous sequences and promote DNA strand exchange has long been known, as are the crystal structures of the RecA-DNA pre- and postsynaptic complexes; however, little is known about the homology searching conformations and the details of how DNA in bacterial genomes is rapidly searched until homologous alignment is achieved. By integrating a physical model of recognition to new modeling work based on docking exploration and molecular dynamics simulation, we present a detailed structure/function model of homology recognition that reconciles extremely quick searching with the efficient and stringent formation of stable strand exchange products and which is consistent with a vast body of previously unexplained experimental results.

}, doi = {10.1093/nar/gkv883}, author = {Yang, Darren and Boyer, Benjamin and Chantal Pr{\'e}vost and Danilowicz, Claudia and Prentiss, Mara} } @article {2015|1965, title = {An integrative approach to the study of filamentous oligomeric assemblies, with application to {R}ec{A}}, journal = {Plos One}, volume = {in press}, year = {2015}, pages = {e0116414}, abstract = {

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

}, doi = {10.1371/journal.pone.0116414}, author = {Benjamin Boyer and Johann Ezelin and Pierre Poulain and A Saladin and Martin Zacharias and Charles H. Robert and Chantal Pr{\'e}vost} } @article {2015|1586, title = {Investigating the Structural Variability and Binding Modes of the Glioma Targeting NFL-TBS.40-63 Peptide on Tubulin}, journal = {Biochemistry}, volume = {54}, number = {23}, year = {2015}, month = {jun}, pages = {3660{\textendash}3669}, doi = {10.1021/acs.biochem5b00146}, author = {Laurin, Y. and Savarin, P. and Charles H. Robert and M. Takahashi and Eyer, J. and Chantal Pr{\'e}vost and S Sacquin-Mora} } @article {2015|1975, title = {{A}llosteric and hyperekplexic mutant phenotypes investigated on an α1 glycine receptor transmembrane structure}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {112}, number = {9}, year = {2015}, month = {mar}, pages = {2865{\textendash}2870}, author = {Moraga-Cid, G. and Sauguet, L. and Huon, C. and Malherbe, L. and Girard-Blanc, C. and Petres, S. and Murail, S. and Antoine Taly and Marc Baaden and Delarue, M. and Corringer, P. J.} } @article {2015|1549, title = {{N}othing to sneeze at: a dynamic and integrative computational model of an influenza {A} virion}, journal = {Structure}, volume = {23}, number = {3}, year = {2015}, month = {mar}, pages = {584{\textendash}597}, author = {Reddy, T. and Shorthouse, D. and Parton, D. L. and Jefferys, E. and Fowler, P. W. and Matthieu Chavent and Marc Baaden and Sansom, M. S.} } @article {2015|1449, title = {{P}redicting and exploring complex nucleic acids architectures through a coarse-grained model}, journal = {J. Biomol. Struct. Dyn.}, volume = {33 Suppl 1}, year = {2015}, pages = {30{\textendash}31}, author = {Cragnolini, T. and Doutreligne, S. and Marc Baaden and Philippe Derreumaux and Pasquali, S.} } @article {2015|1732, title = {The poor homology stringency in the heteroduplex allows strand exchange to incorporate desirable mismatches without sacrificing recognition in vivo}, journal = {Nucleic Acids Res.}, volume = {43}, year = {2015}, month = {jul}, pages = {6473{\textendash}85}, abstract = {

RecA family proteins are responsible for homology search and strand exchange. In bacteria, homology search begins after RecA binds an initiating single-stranded DNA (ssDNA) in the primary DNA-binding site, forming the presynaptic filament. Once the filament is formed, it interrogates double-stranded DNA (dsDNA). During the interrogation, bases in the dsDNA attempt to form Watson-Crick bonds with the corresponding bases in the initiating strand. Mismatch dependent instability in the base pairing in the heteroduplex strand exchange product could provide stringent recognition; however, we present experimental and theoretical results suggesting that the heteroduplex stability is insensitive to mismatches. We also present data suggesting that an initial homology test of 8 contiguous bases rejects most interactions containing more than 1/8 mismatches without forming a detectable 20 bp product. We propose that, in vivo, the sparsity of accidental sequence matches allows an initial 8 bp test to rapidly reject almost all non-homologous sequences. We speculate that once the initial test is passed, the mismatch insensitive binding in the heteroduplex allows short mismatched regions to be incorporated in otherwise homologous strand exchange products even though sequences with less homology are eventually rejected.

}, doi = {10.1093/nar/gkv610}, author = {Danilowicz, Claudia and Yang, Darren and Kelley, Craig and Chantal Pr{\'e}vost and Prentiss, Mara} } @article {2015|1701, title = {Predicting and exploring complex nucleic acids architectures through a coarse-grained model}, journal = {Journal of Biomolecular Structure \& Dynamics}, volume = {33}, year = {2015}, pages = {30{\textendash}31}, doi = {10.1080/07391102.2015.1032593}, author = {Cragnolini, T. and Doutreligne, S. and Marc Baaden and Philippe Derreumaux and Pasquali, S.} } @article {2015|1641, title = {Structure/function relationships in RecA protein-mediated homology recognition and strand exchange}, journal = {Crit. Rev. Biochem. Mol. Biol.}, volume = {50}, year = {2015}, pages = {453{\textendash}76}, abstract = {RecA family proteins include RecA, Rad51, and Dmc1. These recombinases are responsible for homology search and strand exchange. Homology search and strand exchange occur during double-strand break repair and in eukaryotes during meiotic recombination. In bacteria, homology search begins when RecA binds an initiating single-stranded DNA (ssDNA) in the primary DNA-binding site to form the presynaptic filament. The filament is a right-handed helix, where the initiating strand is bound deep within the filament. Once the presynaptic filament is formed, it interrogates nearby double-stranded DNA (dsDNA) to find a homologous sequence; therefore, we provide a detailed discussion of structural features of the presynaptic filament that play important functional roles. The discussion includes many diagrams showing multiple filament turns. These diagrams illustrate interactions that are not evident in single turn structures. The first dsDNA interactions with the presynaptic filament are insensitive to mismatches. The mismatch insensitive interactions lead to dsDNA deformation that triggers a homology testing process governed by kinetics. The first homology test involves {\^a}ˆ{\textonequarter}8 bases. Almost all interactions are rejected by this initial rapid test, leading to a new cycle of homology testing. Interactions that pass the initial rapid test proceed to a slower testing stage. That slower stage induces nonhomologous dsDNA to reverse strand exchange and begin a new cycle of homology testing. In contrast, homologous dsDNA continues to extend the heteroduplex strand-exchange product until ATP hydrolysis makes strand exchange irreversible.}, keywords = {Double-strand break repair, meiosis, meiotic recombination, Rad51, recombinase}, doi = {10.3109/10409238.2015.1092943}, author = {Prentiss, Mara and Chantal Pr{\'e}vost and Danilowicz, Claudia} } @article {2015|1414, title = {{T}hree-dimensional representations of complex carbohydrates and polysaccharides{\textendash}{S}weet{U}nity{M}ol: a video game-based computer graphic software}, journal = {Glycobiology}, volume = {25}, number = {5}, year = {2015}, month = {may}, pages = {483{\textendash}491}, author = {Perez, S. and Tubiana, T. and Imberty, A. and Marc Baaden} } @conference {2015|1555, title = {UnityMol: interactive and ludic visual manipulation of coarse-grained RNA and other biomolecules}, booktitle = {Virtual and Augmented Reality for Molecular Science (VARMS@IEEEVR), 2015 IEEE 1st International Workshop on}, year = {2015}, month = {mar}, pages = {1{\textendash}6}, keywords = {biomolecular systems, coarse-grained RNA, collaborative research applications, data visualisation, feature extracti, HireRNA physics engine, interactive systems, Ludic visual manipulation, molecular biophysics, RNA, software architecture, teaching, UnityMol framework}, author = {S. Doutreligne and C. Gageat and T. Cragnolini and Antoine Taly and S. Pasquali and Philippe Derreumaux and Marc Baaden} } @conference {2015|1408, title = {Visualization of Biomolecular Structures: State of the Art}, booktitle = {Eurographics Conference on Visualization (EuroVis) - STARs}, year = {2015}, publisher = {The Eurographics Association}, organization = {The Eurographics Association}, author = {Kozlikova, Barbora and Krone, Michael and Lindow, Norbert and Falk, Martin and Marc Baaden and Baum, Daniel and Viola, Ivan and Parulek, Julius and Hege, Hans-Christian}, editor = {R. Borgo and F. Ganovelli and I. Viola} } @proceedings {2014|1577, title = {{BIOIMAGING} 2014 - Proceedings of the International Conference on Bioimaging, ESEO, Angers, Loire Valley, France, 3-6 March, 2014}, year = {2014}, publisher = {SciTePress}, editor = {M{\'a}rio Forjaz Secca and Jan Schier and Guy Plantier and Tanja Schultz and Ana L. N. Fred and Hugo Gamboa} } @conference {2014|1784, title = {Coarse-Grain RNA Folding: Towards More Complex Structures}, booktitle = {Biophys. J.}, volume = {106}, number = {2, 1}, year = {2014}, note = {58th Annual Meeting of the Biophysical-Society, San Francisco, CA, FEB 15-19, 2014}, month = {jan}, pages = {283A}, author = {Cragnolini, Tristan and Laurin, Yoann and Philippe Derreumaux and Pasquali, Samuela} } @article {2014|1412, title = {{E}xa{V}iz: a flexible framework to analyse, steer and interact with molecular dynamics simulations}, journal = {Faraday Discuss.}, volume = {169}, year = {2014}, note = {[DOI:\href{http://dx.doi.org/10.1039/c3fd00142c}{10.1039/c3fd00142c}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25340956}{25340956}]}, pages = {119{\textendash}142}, author = {Dreher, M and Prevoteau-Jonquet, J and Trellet, M and Piuzzi, M and Marc Baaden and Raffin, B and Nicolas F{\'e}rey and Robert, S and Limet, S.} } @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} } @article {2014|1518, title = {{T}he weak, fluctuating, dipole moment of membrane-bound hydrogenase from {A}quifex aeolicus accounts for its adaptability to charged electrodes}, journal = {Phys. Chem. Chem. Phys.}, volume = {16}, number = {23}, year = {2014}, month = {may}, pages = {11318{\textendash}11322}, author = {Oteri, F and Ciaccafava, A and Poulpiquet, A and Marc Baaden and Lojou, E and S Sacquin-Mora} } @conference {2014|1496, title = {UnityMol: Interactive scientific visualization for integrative biology}, booktitle = {Large Data Analysis and Visualization (LDAV), 2014 IEEE 4th Symposium on}, year = {2014}, month = {nov}, pages = {109{\textendash}110}, keywords = {biology computing, biomolecular system visualization, data analysis, data exploration, data representation, data visualisation, information extraction, integrative biology, interactive scientific visualization, interactive virtual lab, molecular biophysics, UnityMol}, author = {S. Doutreligne and T. Cragnolini and S. Pasquali and Philippe Derreumaux and Marc Baaden} } @conference {2014|1783, title = {Wide Exploration of OPEP Protein Energy Landscapes using Advanced Monte Carlo Methods}, booktitle = {Biophys. J.}, volume = {106}, number = {2, 1}, year = {2014}, note = {58th Annual Meeting of the Biophysical-Society, San Francisco, CA, FEB 15-19, 2014}, month = {jan}, pages = {256A}, author = {Cragnolini, Tristan and Sutherland-Cash, Kyle H. and Wales, David and Pasquali, Samuela and Philippe Derreumaux} } @article {2013|1699, title = {Agonist-dependent endocytosis of $\gamma$-aminobutyric acid type A (GABAA) receptors revealed by a $\gamma$2 (R43Q) epilepsy mutation}, journal = {J. Biol. Chem.}, volume = {288}, number = {39}, year = {2013}, pages = {28254{\textendash}28265}, publisher = {American Society for Biochemistry and Molecular Biology}, author = {Chaumont, Severine and Andr{\'e}, Caroline and Perrais, David and Bou{\'e}-Grabot, Eric and Antoine Taly and Garret, Maurice} } @article {2013|1938, title = {Allosteric signaling and dynamics of the clamshell-like NMDA receptor GluN1 N-terminal domain}, journal = {Nature Structural \& Molecular Biology}, volume = {20}, number = {4}, year = {2013}, pages = {477{\textendash}485}, publisher = {Nature Publishing Group}, author = {Zhu, Shujia and Stroebel, David and Yao, C Andrea and Antoine Taly and Paoletti, Pierre} } @article {2013|1923, title = {Coarse-Grained Simulations of RNA and DNA Duplexes}, journal = {J. Phys. Chem. B}, volume = {117}, number = {27}, year = {2013}, month = {jul}, pages = {8047{\textendash}8060}, doi = {10.1021/jp400786b}, author = {Cragnolini, Tristan and Philippe Derreumaux and Pasquali, Samuela} } @article {2013|1525, title = {{F}ormation of raft-like assemblies within clusters of influenza hemagglutinin observed by {M}{D} simulations}, journal = {Plos Comput. Biol.}, volume = {9}, number = {4}, year = {2013}, month = {apr}, pages = {e1003034}, author = {Parton, D. L. and Tek, A. and Marc Baaden and Sansom, M. S.} } @article {2013|1531, title = {Interactive Molecular Dynamics: Scaling up to Large Systems.}, journal = {Procedia Comput. Sci.}, volume = {18}, year = {2013}, pages = {20{\textendash}29}, doi = {10.1016/j.procs.2013.05.165}, author = {M. Dreher and M. Piuzzi and A. Turki and Matthieu Chavent and Marc Baaden and Nicolas F{\'e}rey and S. Limet and B. Raffin and S. Robert} } @article {2013|1961, title = {Protein-protein interactions in a crowded environment: an analysis via cross-docking simulations and evolutionary information}, journal = {Plos Comput. Biol.}, volume = {9}, number = {12}, year = {2013}, month = {dec}, pages = {e1003369}, doi = {10.1371/journal.pcbi.1003369}, url = {http://hal.inria.fr/hal-00875116}, author = {Lopes, Anne and S Sacquin-Mora and Dimitrova, Viktoriya and Laine, Elodie and Ponty, Yann and Carbone, Alessandra} } @article {2013|1406, title = {{S}tructural basis for ion permeation mechanism in pentameric ligand-gated ion channels}, journal = {Embo J.}, volume = {32}, number = {5}, year = {2013}, month = {mar}, pages = {728{\textendash}741}, author = {Sauguet, L. and Poitevin, F. and Murail, S. and Van Renterghem, C. and Moraga-Cid, G. and Malherbe, L. and Thompson, A. W. and Koehl, P. and Corringer, P. J. and Marc Baaden and Delarue, M.} } @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|1934, title = {{ATTRACT} and {PTOOLS}: {O}pen source programs for protein-protein docking}, journal = {Methods Mol. Biol.}, volume = {819}, year = {2012}, pages = {221{\textendash}232}, abstract = {

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

}, doi = {10.1007/978-1-61779-465-0_15}, author = {Schneider, S. and A Saladin and Fiorucci, S. and Chantal Pr{\'e}vost and Martin Zacharias} } @article {2012|1920, title = {The Coarse-Grained OPEP Force Field for Non-Amyloid and Amyloid Proteins}, journal = {J. Phys. Chem. B}, volume = {116}, number = {30}, year = {2012}, month = {aug}, pages = {8741{\textendash}8752}, doi = {10.1021/jp301665f}, author = {Y Chebaro and Pasquali, Samuela and Philippe Derreumaux} } @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|1458, title = {Mixing atomistic and coarse grain solvation models for MD simulations: let WT4 handle the bulk}, journal = {Jctc}, year = {2012}, month = {jun}, doi = {10.1021/ct3001816}, author = {L. Darre and A. Tek and Marc Baaden and S. Pantano} } @article {2012|1506, title = {A novel Locally Closed Conformation of a Bacterial Pentameric Proton-gated Ion Channel}, journal = {Nature Structural \& Molecular Biology}, year = {2012}, month = {apr}, author = {M. Prevost and L. Sauguet and H. Nury and C. Van Renterghem and C. Huon and F. Poitevin and Marc Baaden and M. Delarue and P.-J. Corringer} } @article {2012|1753, title = {Rate limit of protein elastic response is tether dependent}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {109}, year = {2012}, pages = {14416{\textendash}14421}, abstract = {

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

}, issn = {0027-8424}, author = {Berkovich, R. and Hermans, R. I. and Popa, I. and Guillaume Stirnemann and Garcia-Manyes, S. and Berne, B. J. and Fernandez, J. M.} } @article {2012|1527, title = {{S}tructure-function analysis of the {NFL}-{TBS}.40-63 peptide corresponding to the binding site of tubulin on the light neurofilament subunit}, journal = {Plos One}, volume = {7}, year = {2012}, pages = {e49436}, author = {Berges, R. and Balzeau, J. and Takahashi, M. and Chantal Pr{\'e}vost and Eyer, J.} } @article {2012|1813, title = {Substitutions at residue 211 in the prion protein drive a switch between CJD and GSS syndrome, a new mechanism governing inherited neurodegenerative disorders}, journal = {Hum. Mol. Genet.}, volume = {21}, number = {26}, year = {2012}, month = {dec}, pages = {5417{\textendash}5428}, doi = {10.1093/hmg/dds377}, author = {Katell Peoc{\textquoteright}h and Etienne Levavasseur and Emilien Delmont and Alfonso De Simone Isabelle Laffont-Proust and Nicolas Privat and Y Chebaro and C{\'e}line Chapuis Pierre Bedoucha and Jean-Philippe Brandel and Annie Laquerriere and Jean-Louis Kemeny Jean-Jacques Hauw and Michel Borg and Human Rezaei and Philippe Derreumaux Jean-Louis Laplanche and St{\'e}phane Ha{\"\i}k} } @article {2011|1654, title = {Accounting for large amplitude protein deformation during in silico macromolecular docking}, journal = {Int. J. Mol. Sci.}, volume = {12}, year = {2011}, pages = {1316{\textendash}33}, abstract = {

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

}, keywords = {flexibility, macromolecular docking, protein loops and domains}, doi = {10.3390/ijms12021316}, author = {Bastard, Karine and A Saladin and Chantal Pr{\'e}vost} } @article {2011|1834, title = {{B}inding modes of noncompetitive {G}{A}{B}{A}-channel blockers revisited using engineered affinity-labeling reactions combined with new docking studies}, journal = {J. Agric. Food Chem.}, volume = {59}, number = {7}, year = {2011}, month = {apr}, pages = {2803{\textendash}2807}, author = {Charon, S. and Antoine Taly and Rodrigo, J. and Perret, P. and Goeldner, M.} } @article {2011|1653, title = {On the characterization and selection of diverse conformational ensembles with applications to flexible docking}, journal = {Ieee/acm Trans. Comput. Biol. Bioinform.}, volume = {8}, year = {2011}, pages = {487{\textendash}98}, abstract = {

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

}, doi = {10.1109/TCBB.2009.59}, author = {Loriot, S{\'e}bastien and Sachdeva, Sushant and Bastard, Karine and Chantal Pr{\'e}vost and Fr{\'e}d{\'e}ric Cazals} } @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|1848, title = {Free energy profiles along consensus normal modes provide insight into {HIV}-1 protease flap opening}, journal = {J. Chem. Theor. Comput.}, volume = {7}, year = {2011}, pages = {2348{\textendash}52}, author = {Paulo R. Batista and Gaurav Pandey and Paulo M. Bisch and Paulo G. Pascutti and David Perahia and Charles H. Robert} } @conference {2011, title = {FvNano: A Virtual Laboratory to Manipulate Molecular Systems}, booktitle = {1st IEEE symposium on biological data visualization, Providence, RI @ ieee visweek, 2011, N$\#$ 136}, year = {2011}, url = {http://www.biovis.net/materials/abstracts/BioVispaper136.pdf}, author = {Matthieu Chavent and Marc Piuzzi and Alex Tek and Marc Baaden} } @article {2011|1889, title = {Impact of Thermostats on Folding and Aggregation Properties of Peptides Using the Optimized Potential for Efficient Structure Prediction Coarse-Grained Model}, journal = {J. Chem. Theory Comput.}, volume = {7}, number = {5}, year = {2011}, month = {may}, pages = {1502{\textendash}1510}, doi = {10.1021/ct100619p}, author = {Spill, Yannick G. and Pasquali, Samuela and Philippe Derreumaux} } @article {2011|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 {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|1524, title = {{H}ow cations can assist {D}{N}ase {I} in {D}{N}{A} binding and hydrolysis}, journal = {Plos Comput. Biol.}, volume = {6}, year = {2010}, month = {nov}, pages = {e1001000}, author = {M. Gueroult and D. Picot and J. Abi-Ghanem and B. Hartmann and Marc Baaden} } @article {2010|1917, title = {HiRE-RNA: A High Resolution Coarse-Grained Energy Model for RNA}, journal = {J. Phys. Chem. B}, volume = {114}, number = {37}, year = {2010}, month = {sep}, pages = {11957{\textendash}11966}, doi = {10.1021/jp102497y}, author = {Pasquali, Samuela and Philippe Derreumaux} } @article {2010|1788, title = {How does heparin prevent the p{H} inactivation of cathepsin {B}? Allosteric mechanism elucidated by docking and molecular dynamics.}, journal = {Bmc Genomics}, volume = {11, S5}, year = {2010}, author = {Mauricio G.S. Costa and Paulo R. Batista and Cl{\`a}udio S Shida and Charles H. Robert and Paulo M. Bisch and Pedro G. Pascutti} } @article {2010|1512, title = {{M}odeling the early stage of {D}{N}{A} sequence recognition within {R}ec{A} nucleoprotein filaments}, journal = {Nucleic Acids Res.}, volume = {38}, year = {2010}, month = {oct}, pages = {6313{\textendash}6323}, author = {A Saladin and Amourda, C. and Poulain, P. and Nicolas F{\'e}rey and Marc Baaden and Martin Zacharias and Delalande, O. and Chantal Pr{\'e}vost} } @article {2010|1472, title = {Nonequilibrium molecular dynamics simulation of the energy transport through a peptide helix}, journal = {J. Chem. Phys.}, volume = {132}, number = {2}, year = {2010}, month = {jan}, author = {Phuong Hoang Nguyen and Park, Sang-Min and Stock, Gerhard} } @article {2010|1529, title = {{O}ne-microsecond molecular dynamics simulation of channel gating in a nicotinic receptor homologue}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {107}, year = {2010}, month = {apr}, pages = {6275{\textendash}6280}, author = {Nury, H. and Poitevin, F. and Van Renterghem, C. and Changeux, J. P. and Corringer, P. J. and Delarue, M. and Marc Baaden} } @inbook {2010|1758, title = {Protein-Protein Docking}, booktitle = {Protein-Protein Complexes. Analysis, Modeling and Drug Design}, year = {2010}, pages = {147{\textendash}181}, publisher = {Imperial College Press}, organization = {Imperial College Press}, chapter = {6}, author = {A Saladin and Chantal Pr{\'e}vost}, editor = {Martin Zacharias} } @article {2010|1457, title = {{A}tomic structure and dynamics of pentameric ligand-gated ion channels: new insight from bacterial homologues}, journal = {J. Physiol. (lond.)}, volume = {588}, year = {2010}, month = {feb}, pages = {565{\textendash}572}, author = {Corringer, P. J. and Marc Baaden and Bocquet, N. and Delarue, M. and Dufresne, V. and Nury, H. and Prevost, M. and Van Renterghem, C.} } @article {2009|1636, title = {Deforming DNA: from physics to biology}, journal = {Chemphyschem}, volume = {10}, year = {2009}, month = {jul}, pages = {1399{\textendash}404}, abstract = {

The DNA double helix has become a modern icon which symbolizes our understanding of the molecular basis of life. It is less widely recognized that the double helix proposed by Watson and Crick more than half a century ago is a remarkably adaptable molecule that can undergo major conformational rearrangements without being irreversibly damaged. Indeed, DNA deformation is an intrinsic feature of many of the biological processes in which it is involved. Over the last two decades, single-molecule experiments coupled with molecular modeling have transformed our understanding of DNA flexibility, while the accumulation of high-resolution structures of DNA-protein complexes have demonstrated how organisms can exploit this property as a useful feature for preserving, reading, replicating, and packaging the genetic message. In this Minireview we summarize the information now available on the extreme\–and the less extreme\–deformations of the double helix.

}, doi = {10.1002/cphc.200900253}, author = {Chantal Pr{\'e}vost and M. Takahashi and Richard Lavery} } @article {2009|1500, title = {Mean field and the confined single homopolymer}, journal = {Mol. Phys.}, volume = {107}, number = {13}, year = {2009}, pages = {1303{\textendash}1312}, author = {S. Pasquali and J. K. Percus} } @article {2009|1469, title = {Molecular dynamics simulation of cooling: Heat transfer from a photoexcited peptide to the solvent}, journal = {J. Chem. Phys.}, volume = {131}, number = {18}, year = {2009}, month = {nov}, author = {Park, Sang-Min and Phuong Hoang Nguyen and Stock, Gerhard} } @article {2009|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|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|1392, title = {{PT}ools: an opensource molecular docking library.}, journal = {Bmc Struct. Biol.}, volume = {9}, year = {2009}, pages = {27{\textendash}37}, doi = {10.1186/1472-6807-9-27}, author = {A Saladin and Fiorucci, S and Poulain, P and Chantal Pr{\'e}vost and Martin Zacharias} } @article {2009|1495, title = {Sphere versus cylinder: the effect of packing on the structure of nonionic C12E6 micelles}, journal = {Langmuir}, volume = {25}, number = {16}, year = {2009}, pages = {8960{\textendash}7}, author = {Sterpone, Fabio and Briganti, G and Pierleoni, C} } @article {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|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|1662, title = {Insights on protein-DNA recognition by coarse grain modelling}, journal = {J. Comput. Chem.}, volume = {29}, year = {2008}, month = {nov}, pages = {2582{\textendash}92}, abstract = {

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

}, doi = {10.1002/jcc.21014}, author = {Poulain, P and A Saladin and Hartmann, B and Chantal Pr{\'e}vost} } @article {2008|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} } @inbook {2008|1565, title = {Recombination and Meiosis : Models, Means and Evolution Coll. Genome Dynamics \& Stability}, booktitle = {Genome Dynamics \& Stability}, volume = {3}, year = {2008}, pages = {65{\textendash}84}, publisher = {Springer Verlag Berlin Heidleberg}, organization = {Springer Verlag Berlin Heidleberg}, chapter = {Searching for Homology by Filaments of RecA-like Proteins}, author = {Chantal Pr{\'e}vost}, editor = {Richard Egel and Dirk-Henner Lankenau} } @inbook {2008|1651, title = {Searching for Homology by Filaments of RecA-like Proteins}, booktitle = {Genome Dynamics \& Stability}, volume = {Recombination and Meiosis. Models, Means and Evolution}, number = {3}, year = {2008}, pages = {65{\textendash}89}, publisher = {Springer Verlag}, organization = {Springer Verlag}, edition = {Richard Egel and Dirk-Henner Lankenau}, address = {Berlin Heidelberg}, abstract = {

The recombinase proteins of the RecA family perform tasks that are essential for cell survival and for the maintenance of genetic diversity. They are able to rearrange genes in new combinations and to repair DNA double-strand breaks in an almost error-free fashion. Their function in homologous recombination is performed in an original way that has no equivalent in the DNA processing machinery: They form long helical filaments on a target DNA, capable of recognizing homologous DNA sequences in the genome and of exchanging DNA strands. How the DNA sequences are recognized during this process and how the DNA strands are exchanged remain matters of investigation. This chapter reviews the information that has been accumulated on recognition and strand exchange, together with the models that aim at organizing this data, viewed at different levels: that of the nucleus, the molecule, or the atom. Altogether, a picture begins to emerge on a multiscale dimension, which presents the search for homology as a complex process with important dynamic components.

}, author = {Chantal Pr{\'e}vost}, editor = {Richard Egel and Dirk Henner-Lankenau} } @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|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} } @inbook {2007|1774, title = {{F}lexible macromolecular docking: {A}n overview of recent progress}, volume = {Recent Research Adv. in Structural BioInformatics}, year = {2007}, pages = {249{\textendash}274}, publisher = {Research Signpost}, organization = {Research Signpost}, chapter = {10}, author = {K. Bastard and Chantal Pr{\'e}vost}, editor = {A. G. De Brevern} } @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} } @inbook {2007|1563, title = {Recent Research Adv. in Structural BioInformatics}, year = {2007}, pages = {249{\textendash}274}, publisher = {Research signpost, Trivandrum, India}, organization = {Research signpost, Trivandrum, India}, chapter = {Flexible macromolecular docking: An overview of recent progress}, author = {K. Bastard and Chantal Pr{\'e}vost}, editor = {A.G. de Brevern} } @article {2006|1536, title = {Accounting for loop flexibility during protein-protein docking}, journal = {Proteins}, volume = {62}, number = {4}, year = {2006}, month = {mar}, pages = {956{\textendash}969}, author = {Bastard, K and Chantal Pr{\'e}vost and Martin Zacharias} } @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|1943, title = {Hfq variant with altered RNA binding functions}, journal = {Nucleic Acids Res.}, volume = {34}, number = {2}, year = {2006}, pages = {709{\textendash}720}, doi = {10.1093/nar/gkj464}, author = {Ziolkowska, K and Philippe Derreumaux and Folichon, M and Pellegrini, O and Regnier, P and Boni, IV and Hajnsdorf, E} } @article {2006|1450, title = {Mapping a Homopolymer onto a Model Fluid}, journal = {J. Chem. Phys.}, volume = {125}, year = {2006}, pages = {064906}, author = {S. Pasquali and J.K. Percus} } @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} } @article {2006|1658, title = {Odorant Binding and Conformational Dynamics in the Odorant-binding Protein}, journal = {J. Biol. Chem.}, volume = {281}, number = {40}, year = {2006}, month = {oct}, pages = {29929{\textendash}29937}, abstract = {In mammals, the olfactory epithelium secretes odorant-binding proteins (OBPs), which are lipocalins found freely dissolved in the mucus layer protecting the olfactory neurons. OBPs may act as passive transporters of predominantly hydrophobic odorant molecules across the aqueous mucus layer, or they may play a more active role in which the olfactory neuronal receptor recognizes the OBP-ligand complex. To better understand the molecular events accompanying the initial steps in the olfaction process, we have performed molecular dynamics studies of rat and pig OBPs with the odorant molecule thymol. These calculations provide an atomic level description of conformational changes and pathway intermediates that remain difficult to study directly. A series of eight independent molecular dynamics trajectories of rat OBP permitted the observation of a consensus pathway for ligand unbinding and the calculation of the potential of mean force (PMF) along this path. Titration microcalorimetry confirmed the specific binding of thymol to this protein with a strong hydrophobic component. In both rat and pig OBPs we observed lipocalin strand pair opening in the presence of ligand, consistent with potential roles of these proteins in olfactive receptor recognition.}, doi = {10.1074/jbc.M604869200}, author = {Eric Hajjar and David Perahia and Helene D{\'e}bat and Claude Nespoulous and Charles H. Robert} } @article {2006|1827, title = {Structure and dynamics of hydrogen bonds in the interface of a C12E6 spherical micelle in water solution: a MD study at various temperatures}, journal = {J. Phys. Chem. B}, volume = {110}, number = {37}, year = {2006}, pages = {18254{\textendash}61}, author = {Sterpone, Fabio and Pierleoni, Carlo and Briganti, Giuseppe and Marchi, Massimo} } @article {2005|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|1839, title = {Insights into the recognition and association of transmembrane $\alpha$-helices. {T}he free energy of $\alpha$-helix dimerization in glycophorin {A}}, journal = {J. Am. Chem. Soc.}, volume = {127}, number = {23}, year = {2005}, pages = {8478{\textendash}8484}, abstract = {The free energy of alpha-helix dimerization of the transmembrane (TM) region of glycophorin A was estimated from a 125-ns molecular dynamics (MD) simulation in a membrane mimetic. The free energy profile was obtained by allowing the TM helical segments to diffuse reversibly along the reaction pathway. Partition of the potential of mean force into free energy components illuminates the critical steps of alpha-helix recognition and association. At large separations, the TM segments are pushed together by the solvent, allowing initial, but not necessarily native, interhelical interactions to occur. This early recognition stage precedes the formation of native contacts, which is accompanied by a tilt of the helices, characteristic of the dimeric structure. This step is primarily driven by the van der Waals helix-helix interactions. Free energy perturbation calculations of the L75A and I76A point mutations reveal a disruption in helix-helix association due to a loss of favorable dispersion interactions. Additional MD simulations of the native TM dimer and of a single alpha-helix confirm that, prior to association, individual alpha-helices are independently stable, in agreement with the "two-stage" model of integral membrane protein folding.}, doi = {10.1021/ja050581y}, author = {J{\'e}r{\^o}me H{\'e}nin and A. Pohorille and Christophe Chipot} } @article {2005|1476, title = {Membrane protein structure quality in molecular dynamics simulation}, journal = {Journal of Molecular Graphics \& Modelling}, volume = {24}, number = {2}, year = {2005}, note = {International Meeting of the Molecular-Graphics-and-Modelling-Society, Manchester, ENGLAND, 2004}, month = {oct}, pages = {157{\textendash}165}, author = {Law, RJ and Capener, C and Marc Baaden and Bond, PJ and Campbell, J and Patargias, G and Arinaminpathy, Y and Sansom, MSP} } @article {2005|1508, title = {Modular RNA architecture revealed by computational analysis of existing pseudoknots and ribosomal RNAs}, journal = {Nuc. Acids Res.}, volume = {33}, year = {2005}, pages = {1384{\textendash}1398}, author = {S. Pasquali and H.H. Gan and T. Schlick} } @article {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|1537, title = {Conformational sampling and dynamics of membrane proteins from 10-nanosecond computer simulations}, journal = {Proteins: Struct., Funct., Bioinf.}, volume = {57}, number = {4}, year = {2004}, month = {dec}, pages = {783{\textendash}791}, author = {Faraldo-Gomez, JD and Forrest, LR and Marc Baaden and Bond, PJ and Domene, C and Patargias, G and Cuthbertson, J and Sansom, MSP} } @article {2004|1647, title = {Critical role of the C-terminal segment in the maturation and export to the cell surface of the homopentameric $\alpha$7{\textendash}5HT3A receptor}, journal = {Eur. J. Neurosci.}, volume = {20}, number = {8}, year = {2004}, pages = {2022{\textendash}2030}, publisher = {Wiley Online Library}, author = {Pons, S and Sallette, J and Bourgeois, JP and Antoine Taly and Jean-Pierre Changeux and Devillers-Thi{\'e}ry, A} } @article {2004|1807, title = {The C-terminal domain of Escherichia coli Hfq increases the stability of the hexamer}, journal = {Eur. J. Biochem.}, volume = {271}, number = {7}, year = {2004}, month = {apr}, pages = {1258{\textendash}1265}, doi = {10.1111/j.1432-1033.2004.04026.x}, author = {Arluison, V and Folichon, M and Marco, S and Philippe Derreumaux and Pellegrini, O and Seguin, J and Hajnsdorf, E and Regnier, P} } @article {2004|1825, title = {Identification of the subunit-subunit interface of Xenopus Rad51.1 protein: Similarity to RecA}, journal = {J. Mol. Biol.}, volume = {335}, number = {4}, year = {2004}, month = {jan}, pages = {895{\textendash}904}, abstract = {

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

}, author = {Selmane, T and Camadro, JM and Conilleau, S and Fleury, F and Tran, V and Chantal Pr{\'e}vost and Takahashi, M} } @article {2004|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|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|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|1663, title = {Docking macromolecules with flexible segments}, journal = {J. Comput. Chem.}, volume = {24}, year = {2003}, month = {nov}, pages = {1910{\textendash}20}, abstract = {

We address a major obstacle to macromolecular docking algorithms by presenting a new method that takes into account the induced conformational adjustment of flexible loops situated at a protein/macromolecule interface. The method, MC2, is based on a multiple copy representation of the loops, coupled with a Monte Carlo conformational search of the relative position of the macromolecules and their side chain conformations. The selection of optimal loop conformations takes place during Monte Carlo cycling by the iterative adjustment of the weight of each copy. We describe here the parameterization of the method and trials on a protein-DNA complex of known 3-D structure, involving the Drosophila prd paired domain protein and its target oligonucleotide Wenqing, X. et al., Cell 1995, 80, 639. We demonstrate that our algorithm can correctly configure and position this protein, despite its relatively complex interactions with both grooves of DNA.

}, doi = {10.1002/jcc.10329}, author = {Bastard, Karine and Thureau, Aur{\'e}lien and Richard Lavery and Chantal Pr{\'e}vost} } @article {2003|1507, title = {Exploring The Repertoire of RNA Secondary Motifs Using Graph Theory with Implications for RNA Design}, journal = {Nuc. Acids Res.}, volume = {31}, year = {2003}, pages = {2926{\textendash}2943}, author = {H. H. Gan and S. Pasquali and and T. Schlick} } @article {2003|1761, title = {Geometry of the DNA strands within the RecA nucleofilament: role in homologous recombination}, journal = {Q. Rev. Biophys.}, volume = {36}, year = {2003}, month = {nov}, pages = {429{\textendash}53}, abstract = {

Homologous recombination consists of exchanging DNA strands of identical or almost identical sequence. This process is important for both DNA repair and DNA segregation. In prokaryotes, it involves the formation of long helical filaments of the RecA protein on DNA. These filaments incorporate double-stranded DNA from the cell\&$\#$39;s genetic material, recognize sequence homology and promote strand exchange between the two DNA segments. DNA processing by these nucleofilaments is characterized by large amplitude deformations of the double helix, which is stretched by 50\% and unwound by 40\% with respect to B-DNA. In this article, information concerning the structure and interactions of the RecA, DNA and ATP molecules involved in DNA strand exchange is gathered and analyzed to present a view of their possible arrangement within the filament, their behavior during strand exchange and during ATP hydrolysis, the mechanism of RecA-promoted DNA deformation and the role of DNA deformation in the process of homologous recombination. In particular, the unusual characteristics of DNA within the RecA filament are compared to the DNA deformations locally induced by architectural proteins which bind in the DNA minor groove. The possible role and location of two flexible loops of RecA are discussed.

}, author = {Chantal Pr{\'e}vost and M. Takahashi} } @article {2003|1465, title = {Local structure in nematic and isotropic liquid crystals}, journal = {J. Chem. Phys.}, volume = {119}, number = {2}, year = {2003}, month = {jul}, pages = {1214{\textendash}1222}, author = {Phuong, NH and Schmid, F} } @article {2002, title = {Analysis of Protein Sequence/Structure Similarity Relationships}, journal = {Biophys. J.}, volume = {83}, year = {2002}, pages = {2781{\textendash}2791}, author = {H. H. Gan and R. A. Perow and S. Roy and J. Ko, M. Wu, J. Huang and S. Yan and A. Nicoletta and J. Vafai, D. Sun and L. Wang and J. E. Noah and S. Pasquali and T. Schlick} } @article {2002|1402, title = {The direct correlation function in nematic liquid crystals from computer simulation}, journal = {Comput. Phys. Commun.}, volume = {147}, number = {1-2}, year = {2002}, note = {Europhysics Conference on Computational Physics (CCP 2001), AACHEN, GERMANY, SEP 05-08, 2001}, month = {aug}, pages = {350{\textendash}353}, author = {Phuong, NH and Germano, G and Schmid, F} } @article {2002|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 {2001|1463, title = {Elastic constants from direct correlation functions in nematic liquid crystals: A computer simulation study}, journal = {J. Chem. Phys.}, volume = {115}, number = {15}, year = {2001}, month = {oct}, pages = {7227{\textendash}7234}, author = {Phuong, NH and Germano, G and Schmid, F} } @article {2001|1933, title = {Molecular Dynamics Study of Spherical Aggregates of Chain Molecules at Different Degrees of Hydrophilicity in Water Solution}, journal = {Langmuir}, volume = {17}, number = {16}, year = {2001}, pages = {5103{\textendash}5110}, author = {Sterpone, Fabio and Briganti, Giuseppe and Pierleoni, Carlo} } @article {2000|1431, title = {A mechanism for RecA-promoted sequence homology recognition and strand exchange between single-stranded DNA and duplex DNA, via triple-helical intermediates}, journal = {J. Biomol. Struct. Dyn.}, number = {Sp. Iss. S1}, year = {2000}, note = {11th Conversation in Biomolecular Stereodynamics, ALBANY, NEW YORK, JUN 15-19, 1999}, pages = {147{\textendash}153}, author = {Bertucat, G and Lavery, R and Chantal Pr{\'e}vost} } @article {1999|1600, title = {A molecular model for RecA-promoted strand exchange via parallel triple-stranded helices}, journal = {Biophys. J.}, volume = {77}, year = {1999}, month = {sep}, pages = {1562{\textendash}76}, abstract = {

A number of studies have concluded that strand exchange between a RecA-complexed DNA single strand and a homologous DNA duplex occurs via a single-strand invasion of the minor groove of the duplex. Using molecular modeling, we have previously demonstrated the possibility of forming a parallel triple helix in which the single strand interacts with the intact duplex in the minor groove, via novel base interactions (Bertucat et al., J. Biomol. Struct. Dynam. 16:535-546). This triplex is stabilized by the stretching and unwinding imposed by RecA. In the present study, we show that the bases within this triplex are appropriately placed to undergo strand exchange. Strand exchange is found to be exothermic and to result in a triple helix in which the new single strand occupies the major groove. This structure, which can be equated to so-called R-form DNA, can be further stabilized by compression and rewinding. We are consequently able to propose a detailed, atomic-scale model of RecA-promoted strand exchange. This model, which is supported by a variety of experimental data, suggests that the role of RecA is principally to prepare the single strand for its future interactions, to guide a minor groove attack on duplex DNA, and to stabilize the resulting, stretched triplex, which intrinsically favors strand exchange. We also discuss how this mechanism can incorporate homologous recognition.

}, doi = {10.1016/S0006-3495(99)77004-9}, author = {Bertucat, G and Richard Lavery and Chantal Pr{\'e}vost} } @article {1998|1530, title = {Folding and Aggregation of Designed Protein Chains}, journal = {Proc. Natl. Acad. Sci. Usa}, volume = {95}, year = {1998}, pages = {12930{\textendash}1293}, author = {R.A. Broglia and G. Tiana and S. Pasquali and H. E. Roman and E. Vigezzi} } @article {1998|1659, title = {A model for parallel triple helix formation by RecA: single-single association with a homologous duplex via the minor groove}, journal = {J. Biomol. Struct. Dyn.}, volume = {16}, year = {1998}, month = {dec}, pages = {535{\textendash}46}, abstract = {

The nucleoproteic filaments of RecA polymerized on single stranded DNA are able to integrate double stranded DNA in a coaxial arrangement (with DNA stretched by a factor 1.5), to recognize homologous sequences in the duplex and to perform strand exchange between the single stranded and double stranded molecules. While experimental results favor the hypothesis of an invasion of the minor groove of the duplex by the single strand, parallel minor groove triple helices have never been isolated or even modeled, the minor groove offering little space for a third strand to interact. Based on an internal coordinate modeling study, we show here that such a structure is perfectly conceivable when the two interacting oligomers are stretched by a factor 1.5, in order to open the minor groove of the duplex. The model helix presents characteristics that coincide with known experimental data on unwinding, base pair inclination and inter-proton distances. Moreover, we show that extension and unwinding stabilize the triple helix. New patterns of triplet interaction via the minor groove are presented.

}, doi = {10.1080/07391102.1998.10508268}, author = {Bertucat, G and Richard Lavery and Chantal Pr{\'e}vost} } @article {1997|1680, title = {Collective-variable Monte Carlo simulation of DNA}, journal = {J. Comp. Chem.}, volume = {18}, year = {1997}, pages = {2001{\textendash}2011}, author = {H. Gabb and Chantal Pr{\'e}vost and G. Bertucat and Charles H. Robert and Richard Lavery} } @article {1997|1819, title = {Distortions of the DNA double helix induced by 1,3-trans-diamminedichloroplatinum(II)-intrastrand cross-link: An internal coordinate molecular modeling study}, journal = {J. Biomol. Struct. Dyn.}, volume = {14}, number = {6}, year = {1997}, month = {jun}, pages = {703{\textendash}714}, abstract = {

A trans-diamminedichloroplatinum(II) (trans-DDP) intrastrand adduct within the sequence d(TCTG*TG*TC).d(GACACAGA) (where G* represents a platinated guanine) is modeled on the basis of qualitative experimental data concerning global unwinding and curvature as well as information on base pairing. Modeling is performed using the internal coordinate JUMNA program, specific to nucleic acids, and modified to include the possibility of covalently bound ligands. Calibration of the energy functions representing the Pt-N7 bond with guanine is described. The platinum atom and the platinum-nitrogen bonds are parameterized for use in the H{\"u}ckel Del Re method to calculate monopoles at each atom. These monopoles are consistent with the Flex force field included in Jumna. By developing an appropriate minimization protocol we are able to generate stable, distorted three-dimensional structures compatible with the experimental data and including an unusually high global unwinding. No a priori geometric assumptions are made in generating these structures.

}, doi = {10.1080/07391102.1997.10508173}, author = {Chantal Pr{\'e}vost and Boudvillain, M and Beudaert, P and Leng, M and Lavery, R and Vovelle, F} } @article {1996|1666, title = {Finding and visualizing nucleic acid base stacking}, journal = {J Mol Graph}, volume = {14}, number = {1}, year = {1996}, month = {feb}, pages = {6{\textendash}11}, author = {Gabb, H A and Sanghani, S R and Charles H. Robert and Chantal Pr{\'e}vost} } @article {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|1681, title = {Efficient conformational space sampling for nucleosides using internal coordinate Monte-Carlo simulations and a modified furanose description}, journal = {J. Comput. Chem.}, volume = {16}, year = {1995}, month = {jun}, pages = {667{\textendash}680}, chapter = {667}, abstract = {

Internal coordinates can be very helpful in modeling large biomacromolecules because freezing stiffer degrees of freedom, such as bond lengths, strongly reduces the number of variables describing the system. This, however, leads to difficulties in treating flexible rings such as the furanose sugars of nucleic acids or the proline residues of proteins, for which internal coordinates are an overcomplete description. We present here a new, internal coordinate furanose model based on the pseudorotational variables phase and amplitude which avoids having to solve a ring closure problem. The choice of a two- rather than a four-variable description is justified by a detailed analysis of molecular dynamic simulations. The efficiency and accuracy of the method are also demonstrated using extensive Monte Carlo simulations. This method of ring treatment is fast and well adapted to macromolecular simulations. (C) 1995 by John Wiley \& Sons, Inc.

}, issn = {0192-8651}, author = {Gabb, HA and Richard Lavery and Chantal Pr{\'e}vost} } @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, title = {Radiation-induced damages in single- and double-stranded DNA}, journal = {Int. J. Radiat. Biol.}, volume = {67}, year = {1995}, month = {feb}, pages = {169{\textendash}76}, abstract = {

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

}, author = {Isabelle, V and Chantal Pr{\'e}vost and Spotheim-Maurizot, M and Sabattier, R and Charlier, M} } @article {1995|1941, title = {Solution structure of oligonucleotides covalently linked to a psoralen derivative.}, journal = {Nucleic Acids Res.}, volume = {23}, number = {5}, year = {1995}, month = {mar}, pages = {788{\textendash}795}, abstract = {

Psoralen (pso) was attached via its C-5 position to the 5\&$\#$39;-phosphate group of an oligodeoxynucleotide d(TAAGCCG) by a hexamethylene linker (m6). Complex formation between pso-m6-d(TAAGCCG) and the complementary strands d(CGGCTTA)[7-7mer] or d(CGGCTTAT)[7-8mer] was investigated by nuclear magnetic resonance in aqueous solution. Structural informations derived from DQF-COSY and NOESY maps, revealed that the mini double helix adopts a B-form conformation and that the deoxyriboses preferentially adopt a C2\&$\#$39;-endo conformation. The nOe connectivities observed between the protons of the bases or the sugars in each duplex, and the protons of the psoralen and the hexamethylene chain, led us to propose a model involving an equilibrium between two conformations due to different locations of the psoralen. Upon UV-irradiation, the psoralen moiety cross-linked the two DNA strands at the level of 5\&$\#$39;TpA3\&$\#$39; sequences. NMR studies of the single major photo-cross-linked duplex pso-m6-d(TAAGCCG) and d(CGGCTTA) were performed. The stereochemistry of the diadduct is indeed cis-syn at both cyclobutane rings. In addition, the effects of this diadduct on the helical structure are analyzed in detail.

}, keywords = {Base Sequence, chemistry, chemistry/radiation effects, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Psoralens, Solutions}, author = {O. Bornet and Chantal Pr{\'e}vost and F. Vovelle and M. Chassignol and N. T. Thuong and G. Lancelot} } @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 {1993|1628, title = {Persistence analysis of the static and dynamical helix deformations of DNA oligonucleotides: application to the crystal structure and molecular dynamics simulation of d(CGCGAATTCGCG)2}, journal = {Biopolymers}, volume = {33}, year = {1993}, month = {mar}, pages = {335{\textendash}50}, abstract = {

A theory and graphical presentation for the analysis of helix structure and deformations in oligonucleotides is presented. The parameters \"persistence\" and \"flexibility\" as defined in the configurational statistics of polymers of infinite length are reformulated at the oligonucleotide level in an extension of J. A. Schellman\&$\#$39;s method [(1974) Biopolymers, Vol. 17, pp. 217-226], and used as a basis for a systematic \"Persistence Analysis\" of the helix deformation properties for all possible subsequences in the structure. The basis for the analysis is a set of link vectors referenced to individual base pairs, and is limited to sequences exhibiting only perturbed rod-like behavior, i.e., below the threshold for supercoiling. The present application of the method is concerned with a physical model for the angular component of bending, so the link vectors are defined as the unit components of a global helix axis obtained by the procedure \"Curves\" of R. Lavery and H. Sklenar [(1988) J. Biomol. Struct. Dynam., Vol. 6, pp. 63-91; (1989) ibid., Vol. 6, pp. 655-667]. A discussion of the relationship between global bending and relative orientation of base pairs is provided. Our approach is illustrated by analysis of some model oligonucleotide structures with intrinsic kinks, the crystal structure of the dodecamer d(CGCGAATTCGCG)2, and the results of two molecular dynamics simulations on this dodecamer using two variations of the GROMOS force field. The results indicate that essentially all aspects of curvature in short oligonucleotides can be determined, such as the position and orientation of each bend, the sharpness or smoothness, and the location and linearity of subsequences. In the case of molecular dynamics simulations, where a Boltzmann ensemble of structures is analyzed, the spatial extent of the deformations (flexibility) is also considered.

}, doi = {10.1002/bip.360330303}, author = {Chantal Pr{\'e}vost and Louise-May, S and Ravishanker, G and Richard Lavery and Beveridge, D L} } @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 {1991|1593, title = {A combined study of aggregation, membrane affinity and pore activity of natural and modified melittin}, journal = {Biochim. Biophys. Acta}, volume = {1069}, number = {1}, year = {1991}, month = {oct}, pages = {77{\textendash}86}, author = {Stankowski, S and Pawlak, M and Kaisheva, E and Charles H. Robert and Schwarz, G} } @article {1991|1767, title = {Mechanism of the rearrangement of the bicyclo [4.2. 0] octan system to the bicyclo [3.2. 1] octan system}, journal = {Tetrahedron}, volume = {47}, year = {1991}, pages = {229{\textendash}238}, abstract = {

A concerted mechanism has been demonstrated for the rearrangement of a tetracyclic ion including a bicyclo [4.2.0] octan system to hibaol, using a selective deuteration on the migrating bond. The stereochemistry of the selectively introduced deuterium was determined by three routes: 1. comparison of the high field 1H NMR spectra of the deuterated and undeuterated compounds, using double irradiation; 2. high field 1H NMR, coupled with molecular mechanics calculations; 3. two dimensional homo and heteronuclear NMR.

}, doi = {10.1016/S0040-4020(01)80919-4}, url = {http://www.sciencedirect.com/science/article/pii/S0040402001809194}, author = {Bastard, Josette and Do Khac, Duc and Fetizon, Marcel and Chantal Pr{\'e}vost and Beloeil, Jean-Claude} } @conference {1991|1580, title = {Methodological considerations on molecular dynamics simulations of DNA oligonucleotides}, booktitle = {AIP Conference Proceedings}, year = {1991}, month = {oct}, publisher = {AIP}, organization = {AIP}, abstract = {

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

}, doi = {10.1063/1.41314}, author = {Beveridge, DL and Swaminathan, S and Ravishanker, G and Withka, J and Srinivasan, J and Chantal Pr{\'e}vost and Louise-May, S and DiCapua, FM and Bolton, PH} } @article {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|1895, title = {THE USE OF ULTRAVIOLET RESONANCE RAMAN INTENSITIES TO TEST PROPOSED MOLECULAR-FORCE FIELDS FOR NUCLEIC-ACID BASES}, journal = {J. Comput. Chem.}, volume = {12}, number = {6}, year = {1991}, month = {jul}, pages = {731{\textendash}741}, doi = {10.1002/jcc.540120610}, author = {LAGANT, P and Philippe Derreumaux and VERGOTEN, G and PETICOLAS, W} } @article {1989|1912, title = {CONFORMATIONAL STUDIES OF NEUROACTIVE LIGANDS .1. FORCE-FIELD AND VIBRATIONAL-SPECTRA OF CRYSTALLINE ACETYLCHOLINE}, journal = {J. Phys. Chem.}, volume = {93}, number = {4}, year = {1989}, month = {feb}, pages = {1338{\textendash}1350}, doi = {10.1021/j100341a033}, author = {Philippe Derreumaux and WILSON, KJ and VERGOTEN, G and PETICOLAS, WL} } @article {1989|1913, title = {CONFORMATIONAL STUDIES OF NEUROACTIVE LIGANDS .2. SOLUTION-STATE CONFORMATIONS OF ACETYLCHOLINE}, journal = {J. Phys. Chem.}, volume = {93}, number = {4}, year = {1989}, month = {feb}, pages = {1351{\textendash}1357}, doi = {10.1021/j100341a034}, author = {WILSON, KJ and Philippe Derreumaux and VERGOTEN, G and PETICOLAS, WL} } @article {1989|1796, title = {RAMAN-SPECTROSCOPY, MOLECULAR-FORCE FIELDS, AND THE DYNAMICS OF BIOLOGICAL MOLECULES}, journal = {Chemica Scripta}, volume = {29A}, year = {1989}, month = {sep}, pages = {113{\textendash}122}, author = {PETICOLAS, WL and WILSON, KJ and Philippe Derreumaux and VERGOTEN, G} } @inbook {1989|1579, title = {Stereospecific Ion-Molecule reactions in the collision cell induced by nucleophilic gas phase reagents on CI/NH4+ protonated diastereoisomeric tetracyclic terpenes.}, booktitle = {Advances in Mass Spectrometry}, volume = {11}, year = {1989}, pages = {1056}, edition = {P. Longevialle, Heyden and Son, Ed, New York}, author = {Cole, RB and Chantal Pr{\'e}vost and Tabet, JC} } @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 {1988|1625, title = {Uv Resonance Raman-spectra and Solution State Conformations of Cholinergic Neurotransmitters}, journal = {Biophys. J.}, volume = {53}, number = {2}, year = {1988}, month = {feb}, pages = {A287-A287}, author = {WILSON, K. J. and Philippe Derreumaux and VERGOTEN, G. and W. L. Peticolas} } @inbook {1987, title = {Calorimetric analysis of oxygen binding to lobster hemocyanin}, booktitle = {Invertebrate Oxygen Carriers}, year = {1987}, publisher = {Springer-Verlag}, organization = {Springer-Verlag}, address = {Berlin}, author = {Parody-Morreale, A. and Robert, C. H. and Gill, S. J.} } @article {1987|1818, title = {Calorimetric studies of oxygen and carbon monoxide binding to human hemoglobin. Sequential binding heats for oxygen}, journal = {J. Biol. Chem.}, volume = {262}, number = {23}, year = {1987}, month = {aug}, pages = {10994{\textendash}10999}, author = {Parody-Morreale, A and Robert, C H and Bishop, G A and Gill, S J} } @article {1987|1991, title = {Gas-solution microcalorimeter for determining heat binding curves}, journal = {Rev. Sci. Instr.}, volume = {58}, year = {1987}, pages = {632{\textendash}638}, author = {Bishop, G. A. and Parody-Morreale, A. and Robert, C. and and Gill, S. J.} } @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} }