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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

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

We investigate the maximum caliber variational principle as an inference algorithm used to predict dynamical properties of complex nonequilibrium, stationary, statistical systems in the presence of incomplete information. Specifically, we…

Statistical Mechanics · Physics 2016-12-28 Carlo Cafaro , Sean Alan Ali

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

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

The weighted ensemble (WE) simulation strategy provides unbiased sampling of non-equilibrium processes, such as molecular folding or binding, but the extraction of rate constants relies on characterizing steady state behavior.…

Statistical Mechanics · Physics 2020-10-02 Jeremy Copperman , Daniel Zuckerman

Markov state models (MSMs) are valuable for studying dynamics of protein conformational changes via statistical analysis of molecular dynamics (MD) simulations. In MSMs, the complex configuration space is coarse-grained into conformational…

Biological Physics · Physics 2024-06-11 Dedi Wang , Yunrui Qiu , Eric Beyerle , Xuhui Huang , Pratyush Tiwary

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

We present a principled approach for estimating the matrix of microscopic rates among states of a Markov process, given only its stationary state population distribution and a single average global kinetic observable. We adapt Maximum…

Statistical Mechanics · Physics 2014-02-17 Purushottam D. Dixit , Ken A. Dill

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

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

Motivated by disease progression-related studies, we propose an estimation method for fitting general non-homogeneous multi-state Markov models. The proposal can handle many types of multi-state processes, with several states and various…

Methodology · Statistics 2024-07-22 Alessia Eletti , Giampiero Marra , Rosalba Radice

The prediction of protein stability changes following single-point mutations plays a pivotal role in computational biology, particularly in areas like drug discovery, enzyme reengineering, and genetic disease analysis. Although…

Quantitative Methods · Quantitative Biology 2025-05-01 Ivan Rossi , Guido Barducci , Tiziana Sanavia , Paola Turina , Emidio Capriotti , Piero Fariselli

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

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

Molecular Dynamics (MD) is a powerful computational microscope for probing protein functions. However, the need for fine-grained integration and the long timescales of biomolecular events make MD computationally expensive. To address this,…

Machine Learning · Computer Science 2026-03-30 Kacper Kapuśniak , Cristian Gabellini , Michael Bronstein , Prudencio Tossou , Francesco Di Giovanni

We use Markov state models (MSMs) to analyze the dynamics of a $\beta$-hairpin-forming peptide in Monte Carlo (MC) simulations with interacting protein crowders, for two different types of crowder proteins [bovine pancreatic trypsin…

Biological Physics · Physics 2018-02-07 Daniel Nilsson , Sandipan Mohanty , Anders Irbäck

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

Markov state models (MSMs) have become a popular approach for investigating the conformational dynamics of proteins and other biomolecules. MSMs are typically built from numerous molecular dynamics simulations by dividing the sampled…

Biomolecules · Quantitative Biology 2015-06-12 Yuan Yao , Raymond Z. Cui , Gregory R. Bowman , Daniel Silva , Jian Sun , Xuhui Huang
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