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Markov State Models (MSM) are widely used to elucidate dynamic properties of molecular systems from unbiased Molecular Dynamics (MD). However, the implementation of reweighting schemes for MSMs to analyze biased simulations, for example…

Chemical Physics · Physics 2020-11-26 Stefanie Kieninger , Luca Donati , Bettina G. Keller

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

Synthetic molecular dynamics (synMD) trajectories from learned generative models have been proposed as a useful addition to the biomolecular simulation toolbox. The computational expense of explicitly integrating the equations of motion in…

Computational Physics · Physics 2022-05-05 John D. Russo , Daniel M. Zuckerman

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

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

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

Molecular Dynamics (MD) simulations are fundamental computational tools for the study of proteins and their free energy landscapes. However, sampling protein conformational changes through MD simulations is challenging due to the relatively…

Biomolecules · Quantitative Biology 2023-07-20 Diego E. Kleiman , Hassan Nadeem , Diwakar Shukla

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 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

Many state of the art methods for the thermodynamic and kinetic characterization of large and complex biomolecular systems by simulation rely on ensemble approaches, where data from large numbers of relatively short trajectories are…

Data Analysis, Statistics and Probability · Physics 2017-04-05 Feliks Nüske , Hao Wu , Jan-Hendrik Prinz , Christoph Wehmeyer , Cecilia Clementi , Frank Noé

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

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

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

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

Molecular simulations can provide microscopic insight into the physical and chemical driving forces of complex molecular processes. Despite continued advancement of simulation methodology, model errors may lead to inconsistencies between…

Chemical Physics · Physics 2016-02-12 Joseph F. Rudzinski , Kurt Kremer , Tristan Bereau

Non-equilibrium Markov State Modeling (MSM) has recently been proposed [Phys. Rev. E 94, 053001 (2016)] as a possible route to construct a physical theory of sliding friction from a long steady state atomistic simulation: the approach…

Statistical Mechanics · Physics 2017-10-17 M. Teruzzi , F. Pellegrini , A. Laio , E. Tosatti

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

Interest in equilibrium-based sampling methods has grown with recent advances in computational hardware and Markov state modeling (MSM) methods, yet outstanding questions remain that hinder widespread adoption. Namely, how do sampling…

Biomolecules · Quantitative Biology 2018-05-15 Maxwell I. Zimmerman , Justin R. Porter , Xianqiang Sun , Roseane R. Silva , Gregory R. Bowman

Molecular dynamics (MD) simulations can model the interactions between macromolecules with high spatiotemporal resolution but at a high computational cost. By combining high-throughput MD with Markov state models (MSMs), it is now possible…

Chemical Physics · Physics 2018-06-13 Manuel Dibak , Mauricio J. del Razo , David De Sancho , Christof Schütte , Frank Noé

State-free reversible VAMPnets (SRVs) are a neural network-based framework capable of learning the leading eigenfunctions of the transfer operator of a dynamical system from trajectory data. In molecular dynamics simulations, these…

Biological Physics · Physics 2019-06-13 Hythem Sidky , Wei Chen , Andrew L. Ferguson
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