Work

Adaptive Markov state model estimation using short reseeding trajectories

Year: 2020

Type: article

Abstract: In the last decade, advances in molecular dynamics (MD) and Markov State Model (MSM) methodologies have made possible accurate and efficient estimation of kinetic rates and reactive pathways for complex biomolecular dynamics occurring on slow time scales. A promising approach to enhanced sampling of MSMs is to use "adaptive" methods, in which new MD trajectories are "seeded" preferentially from previously identified states. Here, we investigate the performance of various MSM estimators applied to reseeding trajectory data, for both a simple 1D free energy landscape and mini-protein folding MSMs of WW domain and NTL9(1-39). Our results reveal the practical challenges of reseeding simulations and suggest a simple way to reweight seeding trajectory data to better estimate both thermodynamic and kinetic quantities.

Source: The Journal of Chemical Physics

DOI: 10.1063/1.5142457

Authors: Hongbin Wan, Vincent A. Voelz

Institution: Temple University

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, NIH Office of the Director, National Institute of General Medical Sciences, Division of Computer and Network Systems

Awards: Computer Cluster for Computational Biology and Biophysics, G1639760498, G2337693016, G6568219255, G7589035627