Breaking Timescale Limits : Microsecond-Scale Molecular Dynamics Simulations and Single Molecule FRET on the Allosteric Information Transfer Through Proteins
Vendredi 6 décembre 2019 11:00
- Duree : 1 heure
Lieu : Salle des séminaires de l’IBS - 71, avenue des Martyrs - Grenoble
Orateur : Steffen WOLF (Biomolecular Dynamics, Institute of Physics, Albert-Ludwigs-University Freiburg, Germany)
Ligand binding to proteins and subsequent functional control by structural changes is at the heart of regulation of protein function. The timescales of underlying allosteric processes range from nano- to milliseconds, and thus are challenges for both theoretical and experimental methods. To overcome this challenge, we combined extensive all-atom molecular dynamics simulations on the order of several μs and single molecule FRET experiments, using the 1300 amino acid Heat Shock Protein 90 (Hsp90) dimer as test system. Hsp90 is one of the most conserved heat shock proteins, and besides its role as chaperone for a wide range of substrates serves as regulator for protein kinases. We show how ATP puts the Hsp90 dimer under strain, and forces the protein into an energetically disfavored active folding conformation. Hydrolysis of ATP to ADP + Pi removes the strain, causing a relaxed, inactive conformation. Interestingly, only few amino acids appear to mediate information transfer between nucleotide and the full protein dimer, which follows hierarchical dynamics. Last, I will give an outlook how nonequilibrium simulations and coarse-graining of microscopic dynamics can be used to further accelerate simulation methods, allowing the prediction kinetics for processes that occur on a timescale of μs to minutes, such as protein-ligand binding and unbinding.
Contact : ibs.seminaires@ibs.fr
Discipline évènement : (Biologie / Chimie)
Entité organisatrice : (IBS)
Nature évènement : (Séminaire)
Evènement répétitif : (Séminaire IBS)
Site de l'évènement : Polygone scientifique
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