Berlin 2018 – wissenschaftliches Programm

Bereiche | Tage | Auswahl | Suche | Aktualisierungen | Downloads | Hilfe

BP: Fachverband Biologische Physik

BP 1: Protein Structure and Dynamics

BP 1.11: Vortrag

Montag, 12. März 2018, 12:30–12:45, H 1028

Validation of reaction coordinates describing protein functional motion: combining equilibrium and non-equilibrium MD methods — •Matthias Ernst, Steffen Wolf, and Gerhard Stock — Biomolecular Dynamics, University of Freiburg

Finding low-dimensional reaction coordinates that concisely describe mechanistic details of protein motion is a fundamental and crucial step to understand (and, at a later stage, to manipulate) protein dynamics. Statistical methods like Principal Component Analysis are often used and well understood, but usually not able to causally disentangle local rearrangements that drive some motion and others that are merely correlated or follow it. In my presentation, I will outline a strategy to combine non-equilibrium methods with equilibrium results to challenge and validate reaction coordinates: we use Targeted MD[1] as "molecular tweezer" to induce local rearrangements and explain causal relations between and the overall functional motion. Investigating the prominent PacMan-like hinge-bending motion of T4 Lysozyme, with  2600 atoms a rather small but extensively studied protein, we could show[2] that a so far unrecognized reorientation of actually one single side chain acts as a lock to stabilize and distinguish the open from the closed state and is the cause of the rather long (≈ 10 µs) timescale. We propose and verify a 4-state model for the hinge-bending motion of T4 Lysozyme, which is supported by mutation studies and higher temperature runs.
J.Schlitter, M.Engels, P.Krüger, J.Mol Graph. 1994, 12, 84.
M.Ernst,S.Wolf,G.Stock,J.Chem.Theory Comput.2017,13(10),5076.