@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 {2018|2114, title = {Rayleigh-Plesset equation of the bubble stable cavitation in water: A nonequilibrium all-atom molecular dynamics simulation study}, journal = {The Journal of Chemical Physics}, volume = {148}, year = {2018}, pages = {094505}, author = {Man, Viet Hoang and Li, Mai Suan and Philippe Derreumaux and Phuong Hoang Nguyen} } @article {2018, title = {RecA requires two molecules of Mg2+ ions for its optimal strand exchange activity in vitro}, journal = {Nucleic Acids Res}, volume = {ahead of print}, year = {2018}, month = {Jan}, abstract = {

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

}, doi = {10.1093/nar/gky048}, author = {Kim, Raeyeong and Kanamaru, Shuji and Mikawa, Tsutomu and Chantal Pr{\'e}vost and Ishii, Kentaro and Ito, Kentaro and Uchiyama, Susumu and Oda, Masayuki and Iwasaki, Hiroshi and Kim, Seog K and Takahashi, Masayuki} } @article {2017|2095, title = {Residues of Alpha Helix H3 Determine Distinctive Features of Transforming Growth Factor β3.}, journal = {J Phys Chem B}, volume = {121}, year = {2017}, month = {2017 06 08}, pages = {5483-5498}, abstract = {

Transforming growth factors (TGF-βs) are proteins that regulate cell growth by binding to their receptors. In contrast to transforming growth factor (TGF) β1, TGF-β3 homodimer is believed to exist also in an open conformation, in which both of its monomers are loosely packed against each other. At the origin of this difference is the H3-helix. Its sequence and degree of structuration seem to govern the outcome of TGF dimerization. We docked two monomers of TGF-β3 with intact and altered H3 α-helix against each other using HADDOCK. TGF-β3 monomer with an intact H3-helix exclusively forms closed conformations of homodimer, whereas the open conformation may coexist with the closed one when a part of the H3 α-helix is destabilized. We quantify the difference in its conformational preference for the open versus the closed structure by calculating the binding energy between monomers using the MMPBSA approach. We compare the wild type (wt) TGFβ3/TGFβ1 homodimers in the Protein Data Bank to a swapped mutant where all residues of the H3-helix were mutated to the respective TGFβ1/TGFβ3 sequence. Swapping stabilizes the closed conformation and destabilizes the open conformation of TGFβ3. Further detailed insight is derived from molecular dynamics simulation studies suggesting that Val 61 of the H3-helix may act as an anchor residue for the closed conformation of TGFβ3. Computational alanine scanning mutagenesis confirms that several residues of the H3-helix are the hot residues for the closed conformation of TGFβ3. These observations may bear relevance to general conformational transitions in proteins and specifically in the TGFβ superfamily.

}, keywords = {Molecular Dynamics Simulation, Protein Conformation, alpha-Helical, Transforming Growth Factor beta3}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b01867}, author = {Nayeem, Shahid M and Oteri, Francesco and Marc Baaden and Deep, Shashank} } @article {2015|1677, title = {Recovering protein thermal stability using all-atom Hamiltonian replica-exchange simulations in explicit solvent}, journal = {J. Chem. Theo. Comput.}, volume = {11}, year = {2015}, pages = {5573{\textendash}5577}, abstract = {

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

}, issn = {15499626}, doi = {10.1021/acs.jctc.5b00954}, author = {Guillaume Stirnemann and Fabio Sterpone} } @article {2015|1727, title = {Replica-exchange molecular dynamics simulation for understanding the initial process of amyloid peptide aggregation}, journal = {Mol. Simul.}, volume = {41}, number = {10-12}, year = {2015}, month = {aug}, pages = {1041{\textendash}1044}, author = {Nishikawa, Naohiro and Phuong Hoang Nguyen and Philippe Derreumaux and Okamoto, Yuko} } @article {2015|1668, title = {Role of Internal Water on Protein Thermal Stability: The Case of Homologous G Domains.}, journal = {J. Phys. Chem. B}, volume = {119}, year = {2015}, month = {jul}, pages = {8939{\textendash}49}, abstract = {

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

}, issn = {1520-5207}, doi = {10.1021/jp507571u}, author = {Rahaman, Obaidur and Kalimeri, Maria and Melchionna, Simone and J{\'e}r{\^o}me H{\'e}nin and Fabio Sterpone} } @article {2013|1976, title = {Reassessing buried surface areas in protein-protein complexes.}, journal = {Protein Sci.}, volume = {22}, year = {2013}, month = {aug}, pages = {1453{\textendash}57}, abstract = {

The buried surface area (BSA), which measures the size of the interface in a protein-protein complex may differ from the accessible surface area (ASA) lost upon association (which we call DSA), if conformation changes take place. To evaluate the DSA, we measure the ASA of the interface atoms in the bound and unbound states of the components of 144 protein-protein complexes taken from the Protein-Protein Interaction Affinity Database of Kastritis et al. (2011). We observe differences exceeding 20\%, and a systematic bias in the distribution. On average, the ASA calculated in the bound state of the components is 3.3\% greater than in their unbound state, and the BSA, 7\% greater than the DSA. The bias is observed even in complexes where the conformation changes are small. An examination of the bound and unbound structures points to a possible origin: local movements optimize contacts with the other component at the cost of internal contacts, and presumably also the binding free energy.

}, keywords = {binding free energy, conformation changes, protein-protein interaction, solvent accessible surface}, doi = {10.1002/pro.2330}, author = {Chakravarty, Devlina and Guharoy, Mainak and Robert, Charles H. and Chakrabarti, Pinak and Janin, Jo{\"e}l} } @article {2013|1806, title = {Replica-exchange molecular dynamics simulations of the amyloid-beta(16-22) fragments}, journal = {European Biophysics Journal with Biophysics Letters}, volume = {42}, number = {1}, year = {2013}, note = {9th European-Biophysical-Societies-Association Congress, Lisbon, PORTUGAL, JUL 13-17, 2013}, month = {jul}, pages = {S68}, author = {Nishikawa, N. and Phuong Hoang Nguyen and Philippe Derreumaux and Okamoto, Y.} } @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 {2011|1487, title = {Real Time Observation of Ultrafast Peptide Conformational Dynamics: Molecular Dynamics Simulation vs Infrared Experiment}, journal = {J. Phys. Chem. B}, volume = {115}, number = {44}, year = {2011}, month = {nov}, pages = {13084{\textendash}13092}, author = {Phuong H. Nguyen and Staudt, Heike and Wachtveitl, Josef and Stock, Gerhard} } @inbook {2011|1417, title = {Receptor Flexibility in Ligand Docking and Virtual Screening.}, booktitle = {In-silico lead discovery}, year = {2011}, publisher = {Bentham Science Publishers}, organization = {Bentham Science Publishers}, author = {Maria A. Miteva and Charles H. Robert and J. D. Marechal and David Perahia} } @article {2011|1383, title = {Reorientation and Allied Dynamics in Water and Aqueous Solutions}, journal = {Annu. Rev. Phys. Chem.}, volume = {62}, year = {2011}, pages = {395{\textendash}416}, abstract = {

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

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

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

}, issn = {15206106}, author = {Vartia, Anthony A. and Mitchell-Koch, Katie R. and Guillaume Stirnemann and Laage, Damien and Thompson, Ward H.} } @inbook {2011|1773, title = {Role of packing, hydration and fluctuation on Thermostability}, booktitle = {Thermostable Proteins Structural Stability and Design}, year = {2011}, publisher = {CRC Press - Taylor and Francis}, organization = {CRC Press - Taylor and Francis}, author = {Fabio Sterpone and Simone Melchionna}, editor = {Srikanta Sen and Lennart Nilsson} } @conference {2010|1459, title = {A Rendering Method for Small Molecules up to Macromolecular Systems: HyperBalls Accelerated by Graphics Processors}, booktitle = {JOBIM}, year = {2010}, author = {Matthieu Chavent and A. Vanel and B. L{\'e}vy and B. Raffin and A. Tek and Marc Baaden} } @article {2010|1471, title = {Replica exchange simulation method using temperature and solvent viscosity}, journal = {J. Chem. Phys.}, volume = {132}, number = {14}, year = {2010}, month = {apr}, author = {Phuong Hoang Nguyen} } @article {2009|1443, title = {{R}elating the {D}iffusion of {S}mall {L}igands in {H}uman {N}euroglobin to {I}ts {S}tructural and {M}echanical {P}roperties}, journal = {J. Phys. Chem. B}, volume = {113}, number = {50}, year = {2009}, month = {nov}, pages = {16257{\textendash}16267}, author = {Bocahut, A. and Bernad, S. and Sebban, P. and S Sacquin-Mora} } @article {2009|1830, title = {Replica exchange molecular dynamics simulations of coarse-grained proteins in implicit solvent.}, journal = {J. Phys. Chem. B}, volume = {113}, number = {1}, year = {2009}, month = {jan}, pages = {267{\textendash}274}, keywords = {Amino Acid Sequence, Computer Simulation, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Peptides, Protein Folding, Protein Structure, Proteins, Secondary, Solvents, Temperature, Thermodynamics}, doi = {10.1021/jp805309e}, author = {Y Chebaro and Xiao Dong and Rozita Laghaei and Philippe Derreumaux and Normand Mousseau} } @article {2009|1779, title = {Role of nucleic acid binding in Sir3p-dependent interactions with chromatin fibers.}, journal = {Biochemistry}, volume = {48}, number = {2}, year = {2009}, month = {jan}, pages = {276{\textendash}288}, publisher = {Department of Biological Sciences and Cell Differentiation and Development Center, Marshall University, Huntington, West Virginia 25755, USA.}, abstract = {

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

}, doi = {10.1021/bi801705g}, author = {Nicholas L Adkins and Steve J McBryant and Cotteka N Johnson and Jennifer M Leidy and Christopher L Woodcock and Charles H Robert and Jeffrey C Hansen and Philippe T Georgel} } @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} } @article {2008|1804, title = {Role of the region 23-28 in A beta fibril formation: Insights from simulations of the monomers and dimers of Alzheimer{\textquoteright}s peptides A beta 40 and A beta 42}, journal = {Curr. Alzheimer Res.}, volume = {5}, number = {3}, year = {2008}, month = {jun}, pages = {244{\textendash}250}, doi = {10.2174/156720508784533330}, author = {Melquiond, Adrien and Dong, Xiao and Mousseau, Normand and Philippe Derreumaux} } @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} } @conference {2007|1491, title = {REVIVOS: REalit{\'e} VIrtuelle pour la construction de VOcabulaires Sp{\'e}cialis{\'e}s}, booktitle = {Journ{\'e}es Francophones d{\textquoteright}Ing{\'e}nierie des Connaissances (AFIA-IC 2007)}, year = {2007}, month = {jul}, address = {Grenoble - France}, author = {Nicolas F{\'e}rey and Claire Toffano-Nioche and Oriane Matte-Taillez and Rachid Gherbi and William Turner} } @article {2003|1877, title = {Role of supersecondary structural elements in protein G folding}, journal = {J. Chem. Phys.}, volume = {119}, number = {9}, year = {2003}, month = {sep}, pages = {4940{\textendash}4944}, doi = {10.1063/1.1596891}, author = {Philippe Derreumaux} } @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 {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} }