Dresden 2017 – scientific programme

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BP: Fachverband Biologische Physik

BP 24: Posters - Protein Structure and Dynamics

BP 24.5: Poster

Tuesday, March 21, 2017, 14:00–16:00, P1A

Identification of reaction coordinates for functional dynamics: understanding the molecular pacman T4 Lysozyme — •Matthias Ernst, Steffen Wolf, and Gerhard Stock — Biomolecular Dynamics, University of Freiburg, Germany

T4 Lysozyme is a model system for both experimental and computational investigations of functional protein dynamics. The major functional dynamics is a hinge-bending motion between its two domains which occurs on a timescale of 10-20µs[1]. Yet, the Free energy landscape based on widely applied reaction coordinates like the radius of gyration or the root mean square deviation to the crystal structure shows a barrier that is much too small to explain this timescale. Hence, there must be mechanistic details that require other reaction coordinates.

Using a combination of distance-based principal component analysis[2] on a 50us long equilibrium trajectory of T4L and inverse targeted molecular dynamics simulations[3], we could identify new reaction coordinates describing local structural rearrangements which act as a locking mechanism. We find two intermediate states on the path between "open" and "closed" which slow down the process. Thus, we propose a hierarchical four-state model that can explain the observed timescales semi-quantitatively.
R.B. Yirdaw and H.S. Mchaourab, Biophys.J. 2012, 103(7), 1525.
M. Ernst, F. Sittel and G. Stock, J.Chem.Phys. 2015, 143, 244114.
J. Schlitter, M. Engels and P. Krüger, J.Mol.Graph. 1994, 12, 84.