Year: 2026
Type: preprint
Abstract: Markov state models (MSMs) play a central role in the analysis of molecular dynamics (MD) simulations for biomolecules, and MSM methodologies have been under continual development since their introduction to the field in the early 2000s. MSMs take MD trajectory data as input and produce a more compact, i.e., coarse-grained, and interpretable representation of the system in terms of conformational states and quantitative observables such as the equilibrium populations of states and the timescales of interconverting between states. Numerous strategies and considerable mathematical formalism have been developed to improve coarse-graining in both time and space to enable the most reliable representation of the underlying biomolecular dynamics. Nevertheless, there remains considerable discussion in the literature regarding best practices and MSM limitations, as well as proposals to abandon or extend the first-order Markovian framework in common use. This Roundtable article gathers together diverse opinions from $> 10$ authors active in MSM development, and by design, each author or author group offers a separate contribution. No consensus view is provided. Instead, the article is meant to be a guide for readers wishing to be exposed to a wide set of expert perspectives.
Source: arXiv (Cornell University)
Authors: Zuckerman, Daniel M., Bowman, Gregory R., Caflisch, Amedeo, Dinner, Aaron R., Fadhluddin, Ahmed, Giangreco, Giuseppe, Huang, Xuhui, Keller, Bettina G., Klus, Stefan, Nüske, Feliks, O'Connor, Michael, Rosta, Edina, Schütte, Christof, Stock, Gerhard, Voelz, Vincent, Weare, Jonathan, Mey, Antonia S. J. S.
Institutions: Oregon Health & Science University, University of Pennsylvania, University of Zurich, University of Chicago, University College London, University of Edinburgh, Freie Universität Berlin, Max Planck Institute for Dynamics of Complex Technical Systems, Zuse Institute Berlin, University of Freiburg, Temple University, Courant Institute of Mathematical Sciences, New York University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: FOR 5099: Reduktion der Komplexität von Nichtgleichgewichtssystemen, G3201988028, Rare-event simulation and analysis for elucidating mechanisms of development and disease, Predoctoral Training in Molecular Biophysics, WESTPA: A high-performance framework for simulating at the frontiers of biology, Understanding and controlling protein energy landscapes by combining simulations and experiments
OpenAlex ID: W7223000235