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Direct simulation of biomolecular dynamics in thermal equilibrium is challenging due to the metastable nature of conformation dynamics and the computational cost of molecular dynamics. Biased or enhanced sampling methods may improve the…

Chemical Physics · Physics 2015-06-12 Benjamin Trendelkamp-Schroer , Frank Noe

Nowadays different experimental techniques, such as single molecule or relaxation experiments, can provide dynamic properties of biomolecular systems, but the amount of detail obtainable with these methods is often limited in terms of time…

Computational Physics · Physics 2017-04-19 Giovanni Pinamonti , Jianbo Zhao , David E. Condon , Fabian Paul , Frank Noé , Douglas H. Turner , Giovanni Bussi

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

Small integration time steps limit molecular dynamics (MD) simulations to millisecond time scales. Markov state models (MSMs) and equation-free approaches learn low-dimensional kinetic models from MD simulation data by performing…

Computational Physics · Physics 2020-07-03 Hythem Sidky , Wei Chen , Andrew L. Ferguson

The formalism of state estimation and hidden Markov models (HMMs) can simplify and clarify the discussion of stochastic thermodynamics in the presence of feedback and measurement errors. After reviewing the basic formalism, we use it to…

Statistical Mechanics · Physics 2015-11-13 John Bechhoefer

Markov state models (MSMs) have been broadly adopted for analyzing molecular dynamics trajectories, but the approximate nature of the models that results from coarse-graining into discrete states is a long-known limitation. We show…

Computational Physics · Physics 2021-05-31 John D. Russo , Jeremy Copperman , David Aristoff , Gideon Simpson , Daniel M. Zuckerman

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

Markov State Modeling has recently emerged as a key technique for analyzing rare events in thermal equilibrium molecular simulations and finding metastable states. Here we export this technique to the study of friction, where strongly…

Statistical Mechanics · Physics 2016-11-09 F. Pellegrini , F. P. Landes , A. Laio , S. Prestipino , E. Tosatti

Markov switching models (MSMs) are probabilistic models that employ multiple sets of parameters to describe different dynamic regimes that a time series may exhibit at different periods of time. The switching mechanism between regimes is…

Machine Learning · Statistics 2019-09-13 Silvia Chiappa

Markov state models (MSMs) have been widely used to analyze computer simulations of various biomolecular systems. They can capture conformational transitions much slower than an average or maximal length of a single molecular dynamics (MD)…

Biomolecules · Quantitative Biology 2018-02-14 Anton V. Sinitskiy , Vijay S. Pande

The Journal of Chemical Physics (JCP) article collection on Markov Models of Molecular Kinetics (MMMK) features recent advances developing and using Markov State Models (MSMs) in atomistic molecular simulations and related applications.…

Chemical Physics · Physics 2020-01-08 Frank Noé , Edina Rosta

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

State-space models (SSM) with Markov switching offer a powerful framework for detecting multiple regimes in time series, analyzing mutual dependence and dynamics within regimes, and asserting transitions between regimes. These models…

Methodology · Statistics 2021-06-14 David Degras , Chee-Ming Ting , Hernando Ombao

Rate processes are often modeled using Markov-State Models (MSM). Suppose you know a prior MSM, and then learn that your prediction of some particular observable rate is wrong. What is the best way to correct the whole MSM? For example,…

Statistical Mechanics · Physics 2017-11-09 Purushottam D. Dixit , Ken A. Dill

Ecological systems can often be characterised by changes among a finite set of underlying states pertaining to individuals, populations, communities, or entire ecosystems through time. Owing to the inherent difficulty of empirical field…

Quantitative Methods · Quantitative Biology 2020-11-12 Brett T. McClintock , Roland Langrock , Olivier Gimenez , Emmanuelle Cam , David L. Borchers , Richard Glennie , Toby A. Patterson

Molecular motors and other complex nonequilibrium systems are controlled by large sets of design parameters, and optimizing those parameters requires computing sensitivities -- derivatives of dynamical observables with respect to the…

Statistical Mechanics · Physics 2026-05-12 John Strahan , Todd R. Gingrich

We present a dynamic coarse-graining technique that allows to simulate the mechanical unfolding of biomolecules or molecular complexes on experimentally relevant time scales. It is based on Markov state models (MSM), which we construct from…

Soft Condensed Matter · Physics 2018-08-17 Fabian Knoch , Ken Schäfer , Gregor Diezemann , Thomas Speck

Markov state models (MSMs)---or discrete-time master equation models---are a powerful way of modeling the structure and function of molecular systems like proteins. Unfortunately, MSMs with sufficiently many states to make a quantitative…

Biomolecules · Quantitative Biology 2015-06-03 Gregory R. Bowman

This study address the computational determination of catalytic reaction rates by moving beyond traditional Transition State Theory (TST), addressing its limitations in complex systems. The Hill relation framework, integrated with Adaptive…

Chemical Physics · Physics 2025-11-25 Thomas Pigeon , Manuel Corral Valero , Pascal Raybaud