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Adopting a $300 \, \mu$s-long molecular dynamics (MD) trajectory of the reversible folding of villin headpiece (HP35) published by D. E. Shaw Research, we recently constructed a Markov state model (MSM) of the folding process based on…

Biological Physics · Physics 2025-10-09 Daniel Nagel , Sofia Sartore , Gerhard Stock

Under certain conditions, the dynamics of coarse-grained models of solvated proteins can be described using a Markov state model, which tracks the evolution of populations of configurations. The transition rates among states that appear in…

Soft Condensed Matter · Physics 2022-09-26 Margarita Colberg , Jeremy Schofield

Experiments, in particular on biological systems, typically probe lower-dimensional observables which are projections of high-dimensional dynamics. In order to infer consistent models capturing the relevant dynamics of the system, it is…

Statistical Mechanics · Physics 2025-11-18 Xizhu Zhao , Dmitrii E. Makarov , Aljaž Godec

A Markov state model of the dynamics of a protein-like chain immersed in an implicit hard sphere solvent is derived from first principles for a system of monomers that interact via discontinuous potentials designed to account for local…

Statistical Mechanics · Physics 2015-06-22 Jeremy Schofield , Hanif Bayat

We present a new method that enables the identification and analysis of both transition and metastable conformational states from atomistic or coarse-grained molecular dynamics (MD) trajectories. Our algorithm is presented and studied by…

Chemical Physics · Physics 2017-10-04 Linda Martini , Adam Kells , Gerhard Hummer , Nicolae-Viorel Buchete , Edina Rosta

Markov state models (MSMs) have been demonstrated to be a powerful method for computationally studying intramolecular processes such as protein folding and macromolecular conformational changes. In this article, we present a new approach to…

Biological Physics · Physics 2015-06-18 Matthew R. Perkett , Michael F. Hagan

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…

Biomolecules · Quantitative Biology 2020-01-29 Hongbin Wan , Vincent A. Voelz

In typical single-molecule force spectroscopy experiments the mechanical unfolding of molecular complexes or biomolecules is studied applying a force ramp to one end of the system while the other end is kept fixed in space. The…

Soft Condensed Matter · Physics 2026-05-18 Marco Oestereich , Jürgen Gauss , Gregor Diezemann

With recent advances in structural biology, including experimental techniques and deep learning-enabled high-precision structure predictions, molecular dynamics methods that scale up to large biomolecular systems are required. Current…

Biological Physics · Physics 2022-06-24 Tim Hempel , Simon Olsson , Frank Noé

Discrete-space kinetic models, i.e., Markov state models, have emerged as powerful tools for reducing the complexity of trajectories generated from molecular dynamics simulations. These models require configuration-space representations…

Chemical Physics · Physics 2019-01-30 Joseph F. Rudzinski , Marc Radu , Tristan Bereau

Developing accurate and efficient coarse-grained representations of proteins is crucial for understanding their folding, function, and interactions over extended timescales. Our methodology involves simulating proteins with molecular…

Biomolecules · Quantitative Biology 2023-10-11 Carles Navarro , Maciej Majewski , Gianni de Fabritiis

Molecular dynamics simulations allow to study the structure and dynamics of single biomolecules in microscopic detail. However, many processes occur on time scales beyond the reach of fully atomistic simulations and require coarse-grained…

Statistical Mechanics · Physics 2019-09-04 Fabian Knoch , Thomas Speck

The conformational kinetics of enzymes can be reliably revealed when they are governed by Markovian dynamics. Hidden Markov Models (HMMs) are appropriate especially in the case of conformational states that are hardly distinguishable.…

Quantitative Methods · Quantitative Biology 2009-02-05 A. Kovalev , N. Zarrabi , F. Werz , M. Boersch , Z. Ristic , H. Lill , D. Bald , C. Tietz , J. Wrachtrup

When clustering molecular dynamics (MD) trajectories into a few metastable conformational states, the Markov state models (MSMs) assumption of timescale separation between fast intrastate fluctuations and rarely occurring interstate…

Soft Condensed Matter · Physics 2025-01-17 Sofia Sartore , Franziska Teichmann , Gerhard Stock

A method is proposed to identify target states that optimize a metastability index amongst a set of trial states and use these target states as milestones (or core sets) to build Markov State Models (MSMs). If the optimized metastability…

Statistical Mechanics · Physics 2016-08-03 Enrico Guarnera , Eric Vanden-Eijnden

A Markov state model is a powerful tool that can be used to track the evolution of populations of configurations in an atomistic representation of a protein. For a coarse-grained linear chain model with discontinuous interactions, the…

Soft Condensed Matter · Physics 2024-02-06 Margarita Colberg , Jeremy Schofield

Markov state models (MSMs) have been successful in computing metastable states, slow relaxation timescales and associated structural changes, and stationary or kinetic experimental observables of complex molecules from large amounts of…

Chemical Physics · Physics 2015-06-17 Frank Noe , Hao Wu , Jan-Hendrik Prinz , Nuria Plattner

The modeling of atomistic biomolecular simulations using kinetic models such as Markov state models (MSMs) has had many notable algorithmic advances in recent years. The variational principle has opened the door for a nearly fully automated…

Biological Physics · Physics 2019-11-26 Martin K. Scherer , Brooke E. Husic , Moritz Hoffmann , Fabian Paul , Hao Wu , Frank Noé

Recent advances in deep learning frameworks have established valuable tools for analyzing the long-timescale behavior of complex systems such as proteins. Especially the inclusion of physical constraints, e.g. time-reversibility, was a…

Quantitative Methods · Quantitative Biology 2021-12-22 Andreas Mardt , Frank Noé

Markov state models (MSMs) are a powerful tool to analyze and coarse-grain complex dynamical data into interpretable kinetic processes. This capability is particularly important in heterogeneous catalysis, where a medley of reactants and…

Statistical Mechanics · Physics 2026-05-11 Caitlin A. McCandler , Chatipat Lorpaiboon , Timothy C. Berkelbach , Jutta Rogal
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