Regensburg 2019 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 1: Protein structure and dynamics
BP 1.7: Vortrag
Montag, 1. April 2019, 11:45–12:00, H4
Protein-ligand interaction and hierarchical complex dynamics of Hsp90 — •Steffen Wolf1, Benedikt Sohmen2, Björn Hellenkamp2, Thorsten Hugel2, and Gerhard Stock1 — 1Biomolecular Dynamics, Institute of Physics, Albert Ludwigs University Freiburg, Germany — 2Institute of Physical Chemistry, livMatS and CIBSS, University of Freiburg, Germany
Ligand binding to proteins and subsequent functional control by the appearing structural changes is at the heart of regulation of protein function. As these processes take place on timescales from µs (ligand binding) to hours (ligand off-binding), accessing them via molecular dynamics simulations is challenging, and requires state-of-art unbiased simulations. Here, we report on extensive unbiased all-atom molecular dynamics simulations with the full 1300 amino acid Hsp90 dimer on the order of 25 µs simulated time, and compare these results to recent single molecule FRET experiments. We show how external energy input in the form of ATP puts the protein under strain, and forces the protein into an energetically disfavored active folding confirmation. Interestingly, only few amino acids appears to be responsible to mediate this conformational shift between nucleotide binding pocket and the full protein dimer. Hydrolysis of ATP to ADP+Pi removes this strain from the protein, causing a relaxed, inactive confirmation. The transition of structural information from the nucleotide binding site to the full dimer structure follows hierarchical dynamics, from initial nucleotide/amino acid contact loss on a ns time scale to complex structure changes on the order of 0.1 − 1 µs.