A5034682723- Protein Structure and Dynamics
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- French Urban and Social Studies
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Bioinformatics and Genomic Networks
- Tuberculosis Research and Epidemiology
- Ancient Egypt and Archaeology
- Machine Learning in Bioinformatics
- Advanced Electron Microscopy Techniques and Applications
- Force Microscopy Techniques and Applications
- Theoretical and Computational Physics
- Microbial Natural Products and Biosynthesis
- Bacterial Infections and Vaccines
- HIV Research and Treatment
- Social Sciences and Governance
- Genetics, Bioinformatics, and Biomedical Research
- Biochemical and Structural Characterization
- Spectroscopy and Quantum Chemical Studies
Institut Pasteur
2014-2024
Centre National de la Recherche Scientifique
2014-2024
Université Paris Cité
2008-2024
Centre de Biologie Structurale
2016-2024
Canadian Nautical Research Society
2014-2020
Physiopathologie et Epidémiologie des Maladies Respiratoires
2012
Sorbonne Université
2012
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques
2008-2010
Délégation Paris 5
2009
Descartes (Belgium)
2009
Abstract Motivation: Recent large-scale omics initiatives have catalogued the somatic alterations of cancer cell line panels along with their pharmacological response to hundreds compounds. In this study, we explored these data advance computational approaches that enable more effective and targeted use current future anticancer therapeutics. Results: We modelled 50% growth inhibition bioassay end-point (GI50) 17 142 compounds screened against 59 lines from NCI60 panel (941 831 data-points,...
The ability of pathogens to cause disease depends on their aptitude escape the immune system. Type IV pili are extracellular filamentous virulence factors composed pilin monomers and frequently expressed by bacterial pathogens. As such they major targets for host In human pathogen Neisseria meningitidis, strains expressing class I pilins contain a genetic recombination system that promotes variation sequence is thought aid escape. However, numerous hypervirulent clinical isolates express II...
The determination of protein structures satisfying distance constraints is an important problem in structural biology. Whereas the most common method currently employed simulated annealing, there have been other methods previously proposed literature. Most them, however, are designed to find one solution only. In order explore exhaustively feasible conformational space, we propose here interval Branch-and-Prune algorithm (iBP) solve Distance Geometry Problem (DGP) associated structure...
Group B Streptococcus (GBS) is the major cause of human neonatal infections. A single clone, designated CC17-GBS, accounts for more than 80% meningitis cases, most severe form infection. However, events allowing blood-borne GBS to penetrate brain remain largely elusive. In this study, we identified host transmembrane receptors α5β1 and αvβ3 integrins as ligands Srr2, a CC17-GBS-specific adhesin. Two motifs located in binding region Srr2 were responsible interaction between CC17-GBS these...
Abstract Motivation: Scoring functions provided by the docking software are still a major limiting factor in virtual screening (VS) process to classify compounds. Score analysis of is not able find out all active This due bad estimation ligand binding energies. Making assumption that compounds should have specific contacts with their target display activity, it would be possible discriminate from inactive ones careful interatomic between molecule and target. However, clustering very tedious...
Abstract Replica‐exchange is a powerful simulation method for sampling the basins of rugged energy landscape. The replica‐exchange method's efficient because it allows replicas to perform round trips in temperature space, thereby visiting both low and high temperatures same simulation. However, have diffusive walk trip rate decreases significantly with system size. These drawbacks make convergence even more difficult than already when bigger systems are tackled. Here, we present simple...
We present a new educational initiative called Meet-U that aims to train students for collaborative work in computational biology and bridge the gap between education research. mimics setup of research projects takes advantage most popular tools cloud computing. Students are grouped teams 4–5 people have realize project from A Z answers challenging question biology. promotes "coopetition," as collaborate within across also competition with each other develop best final product. fosters...
Abstract Motivation: Sampling the conformational space of biological macromolecules generates large sets data with considerable complexity. Data-mining techniques, such as clustering, can extract meaningful information. Among them, self-organizing maps (SOMs) algorithm has shown great promise; in particular since its computation time rises only linearly size set. Whereas SOMs are generally used few neurons, we investigate here their behavior numbers neurons. Results: We present a python...
Abstract: Evaluation of docking results is one the most important problems for virtual screening and in silico drug design. Modern approaches identification active compounds a large data set docked molecules use energy scoring functions. One general significant limitations these methods relates to inaccurate binding estimation, which false compounds. Automatic analysis poses using self-organizing maps (AuPosSOM) represents an alternative approach evaluation based on clustering by similarity...
Identifying druggable cavities on a protein surface is crucial step in structure based drug design. The have to present suitable size and shape, as well appropriate chemical complementarity with ligands. We novel cavity prediction method that analyzes results of virtual screening specific ligands or fragment libraries by means Self-Organizing Maps. demonstrate the two thoroughly studied proteins where it successfully identified their active sites (AS) relevant secondary binding (BS)....
Detailed information on hit–target interaction is very valuable for drug discovery efforts and indispensable rational hit to lead optimization. We developed a new approach combining NMR in whole-cells in-cell NMR) docking characterize at the atomic level. By using NMR, we validated target engagement of antituberculosis imidazopyridine amide (IPA) series with subunit b cytochrome bc1:aa3, major respiratory terminal oxidase mycobacteria. The most advanced IPA called Q203 currently clinical...
Protein-protein interactions (PPIs) are key elements in numerous biological pathways and the subject of a growing number drug discovery projects including against infectious diseases. Designing drugs on PPI targets remains difficult task requires extensive efforts to qualify given interaction as an eligible target. To this end, besides evident need determine role PPIs disease-associated their experimental characterization therapeutics targets, prediction capacity be bound by other protein...
ABSTRACT The HIV‐1 integrase is an attractive target for the therapeutics development against AIDS, as no host homologue of this protein has been identified. strand transfer inhibitors (INSTIs), including raltegravir, specifically second catalytic step integration process by binding to DDE motif site and coordinating Mg 2+ ions. Recent X‐ray crystallographic structures integrase/DNA complex from prototype foamy virus allowed investigate role different partners (integrase, DNA, ions,...
Leishmaniases are neglected parasitic diseases in spite of the major burden they inflict on public health. The identification novel drugs and targets constitutes a research priority. For that purpose we used Leishmania infantum initiation factor 4A (LieIF), an essential translation belongs to DEAD-box proteins family, as potential drug target. We modeled its structure identified two binding sites. A virtual screening diverse chemical library was performed for both results were analyzed with...
The VanA D-Ala:D-Lac ligase is a key enzyme in the emergence of high level resistance to vancomycin Enterococcus species and methicillin-resistant Staphylococcus aureus. It catalyzes formation D-Ala-D-Lac instead target, D-Ala-D-Ala, leading production modified, low binding affinity peptidoglycan precursors. Therefore, appears as an attractive target for design new antibacterials overcome resistance. catalytic site delimited by three domains closed ω-loop upon enzymatic reaction. aim present...
We implemented the Self-Organizing Maps algorithm running efficiently on GPUs, and also provide several clustering methods of resulting maps. scripts a use case to cluster macro-molecular conformations generated by molecular dynamics simulations.The method is available GitHub distributed as pip package.
Many proteins exhibit an equilibrium between multiple conformations, some of them being characterized only by low-resolution information. Visiting all conformations is a demanding task for computational techniques performing enhanced but unfocused exploration collective variable (CV) space. Otherwise, pulling structure toward target condition biases the in way difficult to assess. To address this problem, we introduce here soft-ratcheting temperature-accelerated molecular dynamics (sr-TAMD),...
The d-Ala:d-Lac ligase, VanA, plays a critical role in the resistance of vancomycin. Indeed, it is involved synthesis peptidoglycan precursor, to which vancomycin cannot bind. reaction catalyzed by VanA requires opening so-called "ω-loop", so that substrates can enter active site. Here, conformational landscape explored an enhanced sampling approach: temperature-accelerated molecular dynamics (TAMD). Analysis (MD) and TAMD trajectories recorded on permits graphical description structural...
experimentally induced dyspnea of the work/effort type inhibits, in a top-down manner, spinal transmission nociceptive inputs (dyspnea-pain counterirritation). Previous studies have demonstrated that this inhibition can be assessed by measuring flexion reflex (RIII). However, its clinical application is limited because strong discomfort associated with electrical stimuli required to elicit RIII reflex.we examined whether dyspnea-pain counterirritation phenomenon evaluated effect on magnitude...
Hearing relies on the transduction of sound-evoked vibrations into electrical signals, occurring in stereocilia bundle inner ear hair cells. The G protein-coupled receptor (GPCR) ADGRV1 and multi-PDZ protein PDZD7 play a critical role formation function through their scaffolding signaling properties. During cell development, GPCR activity is specifically inhibited by an unknown mechanism. Here, we describe key interactions mediated two N-terminal PDZ domains cytoplasmic domain ADGRV1. Both...