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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

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

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

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

Molecular simulations and biophysical experiments can be used to provide independent and complementary insights into the molecular origin of biological processes. A particularly useful strategy is to use molecular simulations as a modelling…

Chemical Physics · Physics 2019-12-10 Simone Orioli , Andreas Haahr Larsen , Sandro Bottaro , Kresten Lindorff-Larsen

The parametrization of coarse-grained (CG) simulation models for molecular systems often aims at reproducing static properties alone. The reduced molecular friction of the CG representation usually results in faster, albeit inconsistent,…

Chemical Physics · Physics 2016-07-20 Joseph F. Rudzinski , Tristan Bereau

Molecular dynamics simulations have the potential to provide atomic-level detail and insight to important questions in chemical physics that cannot be observed in typical experiments. However, simply generating a long trajectory is…

Chemical Physics · Physics 2015-06-22 Christian R. Schwantes , Robert T. McGibbon , Vijay S. Pande

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

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

We introduce $\pi$-Girsanov, a new method for constructing Markov state models from biased enhanced-sampling molecular dynamics simulations based on Girsanov reweighting. The key idea behind this new method is to separate the reweighting…

Biological Physics · Physics 2026-03-24 Mingyuan Zhang , Yong Wang , Bettina G. Keller , Hao Wu

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

Heterogeneous multiscale methods (HMM) combine molecular accuracy of particle-based simulations with the computational efficiency of continuum descriptions to model flow in soft matter liquids. In these schemes, molecular simulations…

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

Computer simulations generate trajectories at a single, well-defined thermodynamic state point. Statistical reweighting offers the means to reweight static and dynamical properties to different equilibrium state points by means of analytic…

Computational Physics · Physics 2019-12-25 Marius Bause , Timon Wittenstein , Kurt Kremer , Tristan Bereau

From the point of view of statistical mechanics, a full characterisation of a molecular system requires the experimental determination of its possible states, their populations and the respective interconversion rates. Well-established…

Computational Physics · Physics 2020-06-02 Z. Faidon Brotzakis , Michele Vendruscolo , Peter. G. Bolhuis

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

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

We present a procedure for enhanced sampling of molecular dynamics simulations through informed stochastic resetting. Many phenomena, such as protein folding and crystal nucleation, occur over time scales that are inaccessible in standard…

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

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
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