Regensburg 2019 – scientific programme

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BP: Fachverband Biologische Physik

BP 1: Protein structure and dynamics

BP 1.8: Talk

Monday, April 1, 2019, 12:00–12:15, H4

Dynamical Coring of Markov State Models — •Anna Weber, Daniel Nagel, Benjamin Lickert, and Gerhard Stock — Albert Ludwigs University, 79104 Freiburg

The construction of suitable metastable conformational states is fundamental for the description of protein dynamics through Markov state models. These microstates can be generated via density-based clustering algorithms as, e.g., presented by Sittel et al. [J. Chem. Theory Comput. 38, 152 (2017)], resulting in clusters that are cut at the energy barriers. However, the lack of sampling in the transition region combined with the inevitable projection from high dimension onto a low dimensional space, typically leads to a misclassification of points in the transition region. This often causes intrastate fluctuations to be misinterpreted as interstate transitions, causing artificially short life times of the microstates and spoiling calculations of MSM transition rates.

Dynamical coring represents an effective and simple remedy for those problems by requiring the trajectory to spend a minimum time in the new state for a transition to be counted. Adopting molecular dynamics simulations of a well-established biomolecular system (villin headpiece), we demonstrate that coring immensely improves the Markovianity and metastability of the microstates. Providing high structural and temporal resolution, the combination of density-based clustering and dynamical coring is particularly well suited to describe the complex structural dynamics of unfolded biomolecules.