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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

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

A novel approach to simulate simple protein-ligand systems at large time- and length-scales is to couple Markov state models (MSMs) of molecular kinetics with particle-based reaction-diffusion (RD) simulations, MSM/RD. Currently, MSM/RD…

Chemical Physics · Physics 2021-12-10 Mauricio J. del Razo , Manuel Dibak , Christof Schütte , Frank Noé

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

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

Markov state models (MSMs) are widely employed to analyze the kinetics of complex systems. But despite their effectiveness in many applications, MSMs are prone to systematic or statistical errors, often exacerbated by suboptimal…

Data Analysis, Statistics and Probability · Physics 2025-08-12 Yehor Tuchkov , Luke Evans , Sonya M. Hanson , Erik H. Thiede

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

Stochastic kinetic models (SKMs) are increasingly used to account for the inherent stochasticity exhibited by interacting populations of species in areas such as epidemiology, population ecology and systems biology. Species numbers are…

Computation · Statistics 2023-04-06 Tom E. Lowe , Andrew Golightly , Chris Sherlock

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

In this paper we present a novel method for estimating the parameters of a parametric diffusion processes. Our approach is based on a closed-form Maximum Likelihood estimator for an approximating Continuous Time Markov Chain (CTMC) of the…

Methodology · Statistics 2021-08-31 J. L. Kirkby , Dang Nguyen , Duy Nguyen , Nhu Nguyen

We present new algorithms for computing and approximating bisimulation metrics in Markov Decision Processes (MDPs). Bisimulation metrics are an elegant formalism that capture behavioral equivalence between states and provide strong…

Machine Learning · Computer Science 2019-11-22 Pablo Samuel Castro

This paper considers maximum likelihood (ML) estimation in a large class of models with hidden Markov regimes. We investigate consistency of the ML estimator and local asymptotic normality for the models under general conditions which allow…

Statistics Theory · Mathematics 2021-12-07 Demian Pouzo , Zacharias Psaradakis , Martin Sola

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

State space models contain time-indexed parameters, termed states, as well as static parameters, simply termed parameters. The problem of inferring both static parameters as well as states simultaneously, based on time-indexed observations,…

Computation · Statistics 2021-05-28 Anthony Ebert , Pierre Pudlo , Kerrie Mengersen , Paul Wu , Christopher Drovandi

The stochastic dynamics of biochemical reaction networks can be accurately described by discrete-state Markov processes where each chemical reaction corresponds to a state transition of the process. Due to the largeness problem of the state…

Numerical Analysis · Mathematics 2015-10-01 Alexander Andreychenko , Linar Mikeev , Verena Wolf

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 stochastic motions of a diffusing particle contain information concerning the particle's interactions with binding partners and with its local environment. However, accurate determination of the underlying diffusive properties, beyond…

Biological Physics · Physics 2016-12-21 Peter K. Koo , Simon G. J. Mochrie

Finite state space hidden Markov models are flexible tools to model phenomena with complex time dependencies: any process distribution can be approximated by a hidden Markov model with enough hidden states.We consider the problem of…

Statistics Theory · Mathematics 2021-02-16 Luc Lehéricy

Diffusion models have achieved huge empirical success in data generation tasks. Recently, some efforts have been made to adapt the framework of diffusion models to discrete state space, providing a more natural approach for modeling…

Machine Learning · Statistics 2024-02-15 Hongrui Chen , Lexing Ying

Application of the information-theoretic Maximum Caliber principle to the microtrajectories of a two-state system shows that the determination of key dynamical quantities can be mapped onto the evaluation of properties of the 1-D Ising…

Biological Physics · Physics 2010-08-17 Sarah Marzen , Dave Wu , Mandar Inamdar , Rob Phillips