@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 {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 {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 {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|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 {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 {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} }