A5044840019- Protein Structure and Dynamics
- Heat shock proteins research
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Spectroscopy and Quantum Chemical Studies
- RNA Research and Splicing
- thermodynamics and calorimetric analyses
- RNA modifications and cancer
- Estrogen and related hormone effects
- Advanced Thermodynamics and Statistical Mechanics
- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- Mass Spectrometry Techniques and Applications
- nanoparticles nucleation surface interactions
- Lipid Membrane Structure and Behavior
- Computational Drug Discovery Methods
- Microfluidic and Bio-sensing Technologies
- Theoretical and Computational Physics
- Micro and Nano Robotics
- Prion Diseases and Protein Misfolding
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- Peptidase Inhibition and Analysis
- Genetics, Aging, and Longevity in Model Organisms
- Retinoids in leukemia and cellular processes
Université de Montpellier
2016-2024
Centre National de la Recherche Scientifique
2016-2024
Centre de Biologie Structurale
2016-2024
Inserm
2016-2024
Institut de Recherche en Cancérologie de Montpellier
2022-2023
Institut de Génomique Fonctionnelle
2022
Institut Universitaire de France
2022
École Polytechnique Fédérale de Lausanne
2013-2015
Charles Humbert 8
2014
ETH Zurich
2008-2013
We present a method for determining the free-energy dependence on selected number of collective variables using an adaptive bias. The formalism provides unified description which has metadynamics and canonical sampling as limiting cases. Convergence errors can be rigorously easily controlled. parameters simulation tuned so to focus computational effort only physically relevant regions order parameter space. algorithm is tested reconstruction alanine dipeptide landscape.
Abstract Metadynamics is a powerful technique for enhancing sampling in molecular dynamics simulations and reconstructing the free‐energy surface as function of few selected degrees freedom, often referred to collective variables (CVs). In metadynamics, accelerated by history‐dependent bias potential, which adaptively constructed space CVs. Since its first appearance, significant improvements have been made original algorithm, leading an efficient, flexible, accurate method that has found...
Metadynamics is a widely used and successful method for reconstructing the free-energy surface of complex systems as function small number suitably chosen collective variables. This achieved by biasing dynamics system. The bias acting on variables distorts probability distribution other Here we present simple reweighting algorithm recovering unbiased any variable from well-tempered metadynamics simulation. We show efficiency procedure four backbone dihedral angles alanine dipeptide two even...
Membraneless organelles are dynamical cellular condensates formed via biomolecular liquid-liquid phase separation of proteins and RNA molecules. Multiple evidence suggests that in several cases disordered structural scaffolds drive the condensation by forming a dynamic network inter- intramolecular contacts. Despite blooming research activity this field, characterization these entities is very limited, we still do not understand how behavior encoded amino acid sequences scaffolding proteins....
Abstract The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates broad spectrum of (patho)physiological processes in response to numerous substances including pollutants, natural products and metabolites. However, the scarcity structural data precludes understanding how AHR activated by such diverse compounds. Our 2.85 Å structure human indirubin-bound complex with chaperone Hsp90 co-chaperone XAP2, reported herein, reveals closed conformation dimer...
Molecular Dynamics (MD) plays a fundamental role in characterizing protein disordered states that are emerging as crucial actors many biological processes. Here we assess the accuracy of three current force-fields modeling peptides by combining enhanced-sampling MD simulations with NMR data. These generate significantly different conformational ensembles, and AMBER03w [Best Mittal J. Phys. Chem. B 2010, 114, 14916–14923] provides best agreement experiments, which is further improved adding...
Significance Molecular chaperones are a group of proteins that essential for avoiding the aggregation other in crowded cellular environment. Chaperones function by interacting with these substrate different ways. However, it has remained challenge to measure changes occur and understand how prevent misfolding or aggregation. Here we investigate chaperone system keeps protein denatured clamping polypeptide chain. We observe an expansion chain up 30-fold volume owing steric repulsion between...
Abstract Cells possess remarkable control of the folding and entanglement topology long flexible chromosomal DNA molecules. It is thought that structural maintenance chromosome (SMC) protein complexes play a crucial role in this, by organizing DNAs into series loops. Experimental data suggest SMC are able to translocate on DNA, as well pull out lengths via ‘loop extrusion’ process. We describe Brownian loop-capture-ratchet model for translocation loop extrusion based known structural,...
70-kDa Heat shock proteins are ATP-driven molecular chaperones that perform a myriad of essential cellular tasks. Although structural and biochemical studies have shed some light on their functional mechanism, the fundamental issue role energy consumption, due to ATP-hydrolysis, has remained unaddressed. Here we establish clear connection between non-equilibrium nature Hsp70, ATP hydrolysis, determining feature its function, namely high affinity for substrates. Energy consumption can indeed...
Significance The bacterial flagellar motor (BFM) is the rotary powering swimming of many motile bacteria. Many components this molecular machine are dynamic, a property which allows cell to optimize its behavior in accordance with surrounding environment. A prime example stator unit, membrane-bound ion channel that responsible for applying torque rotor. units mechanosensitive, number engaged dependent on viscous load motor. We measure kinetics stators as function and find mechanosensitivity...
We propose a new approach for the umbrella sampling method in molecular dynamics simulations of complex systems. An accelerated slow degrees freedom is achieved by generating single self-adaptive trajectory that tends to span uniformly reaction coordinate using time dependent bias potential derived from preceding history system. To show convergent behavior and efficiency method, we present free energy surface alanine dipeptide water as function backbone dihedral angles.
Significance Oligomeric proteins, comprising two or more associating polypeptide chains, represent a large fraction of cellular proteins. In particular, many proteins self-associate into homooligomers to gain functional advantages. Our understanding the oligomerization at molecular level is currently limited because intermediates that occur in process are short-lived most occasions, precluding direct experimental characterization. Using dynamics simulations, enhanced by sampling method...
Hsp70s are a class of ubiquitous and highly conserved molecular chaperones playing central role in the regulation proteostasis cell. assist myriad cellular processes by binding unfolded or misfolded substrates during complex biochemical cycle involving large-scale structural rearrangements. Here we show that an analysis coevolution at residue level fully captures characteristic conformational transitions this protein family, predicts evolutionary conserved–and thus functional–homo-dimeric...
Hsp70 participates in a broad spectrum of protein folding processes extending from nascent chain to disaggregation. This versatility function is achieved through diverse family J-protein cochaperones that select substrates for Hsp70. Substrate selection further tuned by transient complexation between different classes J-proteins, which expands the range aggregates targeted metazoan We assessed prevalence and evolutionary conservation cooperation find emergence eukaryote-specific signature...
Aromatic residues are located at structurally important sites of many proteins. Probing their interactions and dynamics can provide functional insight but is challenging in large Here, we introduce approaches to characterize the phenylalanine using 1H-detected fast magic-angle spinning (MAS) NMR combined with a tailored isotope-labeling scheme. Our approach yields isolated two-spin systems that ideally suited for artifact-free measurements, allows probing motions effectively without...
In the present study we have used molecular dynamics simulations to stability of antiparallel β-sheet in cellular mouse prion protein (PrPC) and D178N mutant. particular, using recently developed non-Markovian metadynamics method, evaluated free energy as a function reaction coordinate related disruption/growth. We found that is significantly weaker pathogenic mutant than wild-type PrPC. The destabilization PrPC β-structure correlated weakening hydrogen bonding network involving mutated...