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We introduce a path sampling method for obtaining statistical properties of an arbitrary stochastic dynamics. The method works by decomposing a trajectory in time, estimating the probability of satisfying a progress constraint, modifying…

Statistical Mechanics · Physics 2015-06-04 Nicholas Guttenberg , Aaron R. Dinner , Jonathan Weare

Mean-field molecular dynamics based on path integrals is used to approximate canonical quantum observables for particle systems consisting of nuclei and electrons. A computational bottleneck is the sampling from the Gibbs density of the…

Numerical Analysis · Mathematics 2023-11-30 Xin Huang , Petr Plechac , Mattias Sandberg , Anders Szepessy

Sampling the collective, dynamical fluctuations that lead to nonequilibrium pattern formation requires probing rare regions of trajectory space. Recent approaches to this problem based on importance sampling, cloning, and spectral…

Statistical Mechanics · Physics 2022-02-14 Jiawei Yan , Hugo Touchette , Grant M. Rotskoff

The simulation of high-energy physics collision events is a key element for data analysis at present and future particle accelerators. The comparison of simulation predictions to data allows looking for rare deviations that can be due to…

High Energy Physics - Experiment · Physics 2024-07-16 Francesco Vaselli , Filippo Cattafesta , Patrick Asenov , Andrea Rizzi

Activated processes from chemical reactions up to conformational transitions of large biomolecules are hampered by barriers which are overcome only by the input of some free energy of activation. Hence, the characteristic and…

Statistical Mechanics · Physics 2011-12-21 Jürgen Schlitter

In this paper we combine two powerful computational techniques, well-tempered metadynamics and time lagged independent component analysis. The aim is to develop a new tool for studying rare events and exploring complex free energy…

Statistical Mechanics · Physics 2017-12-08 James McCarty , Michele Parrinello

Photo-induced processes are fundamental in nature, but accurate simulations are seriously limited by the cost of the underlying quantum chemical calculations, hampering their application for long time scales. Here we introduce a method…

Binding free energies are a key element in understanding and predicting the strength of protein--drug interactions. While classical free energy simulations yield good results for many purely organic ligands, drugs including transition metal…

The computer simulation of many molecular processes is complicated by long time scales caused by rare transitions between long-lived states. Here, we propose a new approach to simulate such rare events, which combines transition path…

Computational Physics · Physics 2023-03-23 Sebastian Falkner , Alessandro Coretti , Christoph Dellago

Transition path sampling is a method for estimating the rates of rare events in molecular systems based on the gradual transformation of a path distribution containing a small fraction of reactive trajectories into a biased distribution in…

Statistical Mechanics · Physics 2015-10-28 Pierre Terrier , Mihai-Cosmin Marinica , Manuel Athènes

According to the Jarzynski theorem, equilibrium free energy differences can be calculated from the statistics of work carried out during non-equilibrium transformations. Although exact, this approach can be plagued by large statistical…

Statistical Mechanics · Physics 2007-05-23 Wolfgang Lechner , Christoph Dellago

Accurate free-energy calculations are essential for predicting thermodynamic properties and phase stability, but existing methods are limited: phonon-based approaches neglect anharmonicity and liquids, while molecular dynamics (MD) is…

Materials Science · Physics 2025-11-19 Ekaterina Spirande , Timofei Miryashkin , Andrei Kolmakov , Alexander Shapeev

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…

Enhanced sampling methods such as metadynamics and umbrella sampling have become essential tools for exploring the configuration space of molecules and materials. At the same time, they have long faced a number of issues such as the…

Chemical Physics · Physics 2021-12-28 Dongdong Wang , Yanze Wang , Junhan Chang , Linfeng Zhang , Han Wang , Weinan E

Assessing the time scale of biological processes using molecular dynamics (MD) simulations with sufficient statistical accuracy is a challenging task, as processes are often rare and/or slow events, which may extend largely beyond the time…

Computational Physics · Physics 2026-02-16 Wouter Vervust , Elias Wils , Sina Safaei , Daniel T. Zhang , An Ghysels

We apply well-established concepts of Langevin sampling to derive a new class of algorithms for the efficient computation of free energy differences of fluctuating particles embedded in a 'fast' membrane, i.e., a membrane that…

Numerical Analysis · Mathematics 2020-10-01 Tobias Kies , Carsten Gräser , Luigi Delle Site , Ralf Kornhuber

Coarse-graining (CG) enables molecular dynamics (MD) simulations of larger systems and longer timescales that are otherwise infeasible with atomistic models. Machine learning potentials (MLPs), with their capacity to capture many-body…

Chemical Physics · Physics 2025-12-01 Weilong Chen , Franz Görlich , Paul Fuchs , Julija Zavadlav

Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies…

Chemical Physics · Physics 2014-07-29 Viveca Lindahl , Jack Lidmar , Berk Hess

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

Significant progress in computer hardware and software have enabled molecular dynamics (MD) simulations to model complex biological phenomena such as protein folding. However, enabling MD simulations to access biologically relevant…

Biomolecules · Quantitative Biology 2019-08-02 Heng Ma , Debsindhu Bhowmik , Hyungro Lee , Matteo Turilli , Michael T. Young , Shantenu Jha , Arvind Ramanathan