A5076453514- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Bioinformatics and Genomic Networks
- Machine Learning in Bioinformatics
- Microbial Metabolic Engineering and Bioproduction
- Computational Drug Discovery Methods
- Cancer, Hypoxia, and Metabolism
- Bacterial Genetics and Biotechnology
- RNA Research and Splicing
- Bacillus and Francisella bacterial research
- Adipose Tissue and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Genomics and Chromatin Dynamics
- Mast cells and histamine
- Amino Acid Enzymes and Metabolism
- Evolution and Genetic Dynamics
- Genetic Neurodegenerative Diseases
- Biochemical and Molecular Research
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
Laboratoire de Biologie Computationnelle et Quantitative
2016-2025
Sorbonne Université
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Institut Universitaire de France
2023-2024
Institut de Biologie Paris-Seine
2020-2023
Délégation Paris 6
2022
Genomics (United Kingdom)
2018
Laboratoire de Biologie et Pharmacologie Appliquée
2013-2014
Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique
2014
École Normale Supérieure Paris-Saclay
2011-2014
Advances in DNA sequencing and machine learning are providing insights into protein sequences structures on an enormous scale1. However, the energetics driving folding invisible these remain largely unknown2. The hidden thermodynamics of can drive disease3,4, shape evolution5-7 guide engineering8-10, new approaches needed to reveal for every sequence structure. Here we present cDNA display proteolysis, a method measuring thermodynamic stability up 900,000 domains one-week experiment. From...
The systematic and accurate description of protein mutational landscapes is a question utmost importance in biology, bioengineering, medicine. Recent progress has been achieved by leveraging on the increasing wealth genomic data modeling intersite dependencies within biological sequences. However, state-of-the-art methods remain time consuming. Here, we present Global Epistatic Model for predicting Mutational Effects (GEMME) (www.lcqb.upmc.fr/GEMME), an original fast method that predicts...
We present the results for CAPRI Round 46, third joint CASP-CAPRI protein assembly prediction challenge. The comprised a total of 20 targets including 14 homo-oligomers and 6 heterocomplexes. Eight homo-oligomer one heterodimer proteins that could be readily modeled using templates from Protein Data Bank, often available full assembly. remaining 11 5 homodimers, 3 heterodimers, two higher-order assemblies. These were more difficult to model, as their mainly involved "ab-initio" docking...
The type III receptor tyrosine kinase (RTK) KIT plays a crucial role in the transmission of cellular signals through phosphorylation events that are associated with switching protein conformation between inactive and active states. D816V mutation is various pathologies including mastocytosis cancers. D816V-mutated constitutively active, resistant to treatment anti-cancer drug Imatinib. To elucidate activating molecular mechanism this mutation, we applied multi-approach procedure combining...
Allostery plays a key role in the regulation of activity and function many biomolecules. And although ligands act through allostery, no systematic use is made it drug design strategies. Here we describe procedure for identifying regions protein that can be used to control its allostery. This based on construction plausible conformational path, which describes transition between known active inactive conformations. The path calculated by using framework approach steers markedly improves...
A fundamental goal in cellular signaling is to understand allosteric communication, the process by which signals originated at one site a protein propagate dependably affect remote functional sites. Here, we describe regulation of receptor tyrosine kinase KIT. Our analysis evidenced that communication routes established between activation loop (A-loop) and distant juxtamembrane region (JMR) native were disrupted oncogenic mutation D816V positioned A-loop. In silico mutagenesis provided...
Abstract Advances in DNA sequencing and machine learning are illuminating protein sequences structures on an enormous scale. However, the energetics driving folding invisible these remain largely unknown. The hidden thermodynamics of can drive disease, shape evolution, guide engineering, new approaches needed to reveal for every sequence structure. We present cDNA display proteolysis, a method measuring thermodynamic stability up 900,000 domains one-week experiment. From 1.8 million...
Large-scale analyses of protein-protein interactions based on coarse-grain molecular docking simulations and binding site predictions resulting from evolutionary sequence analysis, are possible realizable hundreds proteins with variate structures interfaces. We demonstrated this the 168 Mintseris Benchmark 2.0. On one hand, we evaluated quality interaction signal contribution information compared to showing that combination two improves partner identification. other since protein usually...
Protein-protein interactions (PPIs) are essential to all biological processes and they represent increasingly important therapeutic targets. Here, we present a new method for accurately predicting protein-protein interfaces, understanding their properties, origins binding multiple partners. Contrary machine learning approaches, our combines in rational very straightforward way three sequence- structure-based descriptors of protein residues: evolutionary conservation, physico-chemical...
The spectacular recent advances in protein and complex structure prediction hold promise for reconstructing interactomes at large-scale residue resolution. Beyond determining the 3D arrangement of interacting partners, modeling approaches should be able to unravel impact sequence variations on strength association.In this work, we report Deep Local Analysis, a novel efficient deep learning framework that relies strikingly simple deconstruction interfaces into small locally oriented...
Background: Dissecting the functional impact of genetic mutations is essential to advancing our understanding genotype-phenotype relationships and identifying new therapeutic targets. Despite progress in sequencing CRISPR technologies, proteome-wide mutation effect prediction remains challenging. Here, we introduce ProteoCast, a scalable interpretable computational method for classification variants protein site identification. It relies solely on evolutionary information, leveraging...
<title>Abstract</title> <bold>Background:</bold> Dissecting the functional impact of genetic mutations is essential to advancing our understanding genotype-phenotype relationships and identifying new therapeutic targets. Despite progress in sequencing CRISPR technologies, proteome-wide mutation effect prediction remains challenging. Here, we introduce ProteoCast, a scalable interpretable computational method for classification variants protein site identification. It relies solely on...
Abstract Critical Assessment of Structure Prediction (CASP) is an organization aimed at advancing the state art in computing protein structure from sequence. In spring 2020, CASP launched a community project to compute structures most structurally challenging proteins coded for SARS‐CoV‐2 genome. Forty‐seven research groups submitted over 3000 three‐dimensional models and 700 sets accuracy estimates on 10 proteins. The resulting were released public. members also worked together provide...
The wealth of genomic data has boosted the development computational methods predicting phenotypic outcomes missense variants. most accurate ones exploit multiple sequence alignments, which can be costly to generate. Recent efforts for democratizing protein structure prediction have overcome this bottleneck by leveraging fast homology search MMseqs2. Here, we show usefulness strategy mutational outcome through a large-scale assessment 1.5M variants across 72 families. Our study demonstrates...
Exhaustive experimental annotation of the effect all known protein variants remains daunting and expensive, stressing need for scalable predictions. We introduce VespaG, a blazingly fast missense amino acid variant predictor, leveraging Language Model (pLM) embeddings as input to minimal deep learning model. To overcome sparsity training data, we created dataset 39 million single from human proteome applying multiple sequence alignment-based predictor GEMME pseudo standard-of-truth. This...
Proteins play a central role in biological processes, and understanding their conformational variability is crucial for unraveling functional mechanisms. Recent advancements high-throughput technologies have enhanced our knowledge of protein structures, yet predicting multiple states motions remains challenging. This study introduces Dimensionality Analysis Conformational Exploration (DANCE) systematic comprehensive description families variability. DANCE accommodates both experimental...
Allostery is a universal phenomenon that couples the information induced by local perturbation (effector) in protein to spatially distant regulated sites. Such an event can be described terms of large scale transmission (communication) through dynamic coupling between structurally rigid (minimally frustrated) and plastic (locally clusters residues. To elaborate rational description allosteric coupling, we propose original approach – MOdular NETwork Analysis (MONETA) based on analysis...
The classic model of tumor suppression implies that malignant transformation requires full "two-hit" inactivation a tumor-suppressor gene. However, more recent work in mice has led to the proposal "continuum" involves fluid concepts such as gene dosage-sensitivity and tissue specificity. Mutations von Hippel-Lindau (VHL) are associated with complex spectrum conditions. Homozygotes or compound heterozygotes for R200W germline mutation VHL have Chuvash polycythemia, whereas heterozygous...
Receptor tyrosine kinase KIT controls many signal transduction pathways and represents a typical allosterically regulated protein. The mutation-induced deregulation of activity impairs cellular physiological functions causes serious human diseases. impact hotspots mutations (D816H/Y/N/V V560G/D) localized in crucial regulatory segments, the juxtamembrane region (JMR) activation (A-) loop, on internal dynamics was systematically studied by molecular simulations. mutational outcomes predicted...
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 A novel computational approach of coevolution analysis allowed us to reconstruct the protein-protein interaction network Hepatitis C Virus (HCV) at residue resolution. For first time, an entire viral genome was realized, based on a limited set protein sequences with high sequence identity within genotypes. The identified coevolving residues constitute highly relevant predictions interactions for further experimental identification HCV complexes. method can be used analyse other...
Proteins adapt to environmental conditions by changing their shape and motions. Characterising protein conformational dynamics is increasingly recognised as necessary understand how proteins function. Given a ensemble, computational tools are needed extract in systematic way pertinent comprehensive biological information.Here, we present method, Communication Mapping (COMMA), decipher the dynamical architecture of protein. The method first extracts residue-based dynamic properties from...