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The development of enhanced sampling methods has greatly extended the scope of atomistic simulations, allowing long-time phenomena to be studied with accessible computational resources. Many such methods rely on the identification of an…

Computational Physics · Physics 2022-06-08 Luigi Bonati , GiovanniMaria Piccini , Michele Parrinello

The phenomenon of solidification of a substance from its liquid phase is of the greatest practical and theoretical importance, and atomistic simulations can provide precious information towards its understanding and control. Unfortunately,…

Soft Condensed Matter · Physics 2021-03-25 Tarak Karmakar , Michele Invernizzi , Valerio Rizzi , Michele Parrinello

We describe a method that focuses sampling effort on a user-defined selection of a large system, which can lead to substantial decreases in computational effort by speeding up the calculation of nonbonded interactions. A naive approach can…

Statistical Mechanics · Physics 2023-08-28 Joshua Fass , Forrest York , Matthew Wittmann , Joseph Kaus , Yutong Zhao

Stochastic systems often exhibit multiple viable metastable states that are long-lived. Over very long timescales, fluctuations may push the system to transition between them, drastically changing its macroscopic configuration. In realistic…

Statistical Mechanics · Physics 2023-04-14 Tobias Grafke , Alessandro Laio

Stochastic simulation models effectively capture complex system dynamics but are often too slow for real-time decision-making. Traditional metamodeling techniques learn relationships between simulator inputs and a single output summary…

Machine Learning · Computer Science 2026-01-21 L. Jeff Hong , Yanxi Hou , Qingkai Zhang , Xiaowei Zhang

Molecular dynamics (MD) simulations are useful in obtaining thermodynamic and kinetic properties of bio-molecules but are limited by the timescale barrier, i.e., we may be unable to efficiently obtain properties because we need to run…

Chemical Physics · Physics 2017-08-23 Surl-Hee Ahn , Jay W. Grate , Eric F. Darve

We study how stochastic resetting affects first-passage processes in systems of many interacting particles. While resetting is well understood for single-particle dynamics, its consequences for collective behavior remain less clear. We…

Statistical Mechanics · Physics 2026-04-28 Juhee Lee , Seong-Gyu Yang , Ludvig Lizana

Sampling rare events in metastable dynamical systems is often a computationally expensive task and one needs to resort to enhanced sampling methods such as importance sampling. Since we can formulate the problem of finding optimal…

Optimization and Control · Mathematics 2023-10-05 Enric Ribera Borrell , Jannes Quer , Lorenz Richter , Christof Schütte

The study of the rare transitions that take place between long lived metastable states is a major challenge in molecular dynamics simulations. Many of the methods suggested to address this problem rely on the identification of the slow…

Chemical Physics · Physics 2023-06-07 Dhiman Ray , Enrico Trizio , Michele Parrinello

A new approach for efficiently exploring the configuration space and computing the free energy of large atomic and molecular systems is proposed, motivated by an analogy with reinforcement learning. There are two major components in this…

Chemical Physics · Physics 2018-04-18 Linfeng Zhang , Han Wang , Weinan E

Stochastic restarting is a strategy of starting anew. Incorporation of the resetting to the random walks can result in the decrease of the mean first passage time, due to the ability to limit unfavorably meandering, sub-optimal…

Statistical Mechanics · Physics 2023-11-08 Karol Capała , Bartłomiej Dybiec

A variety of enhanced sampling methods predict multidimensional free energy landscapes associated with biological and other molecular processes as a function of a few selected collective variables (CVs). The accuracy of these methods is…

Computational Physics · Physics 2024-04-09 Lukas Müllender , Andrea Rizzi , Michele Parrinello , Paolo Carloni , Davide Mandelli

In the classical stochastic resetting problem, a particle, moving according to some stochastic dynamics, undergoes random interruptions that bring it to a selected domain, and then, the process recommences. Hitherto, the resetting mechanism…

Statistical Mechanics · Physics 2020-12-08 Carlos A. Plata , Deepak Gupta , Sandro Azaele

The determination of efficient collective variables is crucial to the success of many enhanced sampling methods. As inspired by previous discrimination approaches, we first collect a set of data from the different metastable basins. The…

Computational Physics · Physics 2026-03-03 Enrico Trizio , Michele Parrinello

Stochastic resetting is known for its ability to accelerate search processes and induce non-equilibrium steady states. Here, we compare the relaxation times and resulting steady states of resetting and thermal relaxation for Brownian motion…

Statistical Mechanics · Physics 2025-10-31 Nir Sherf , Remi Goerlich , Barak Hirshberg , Yael Roichman

Controlling polymorphism in molecular crystals is crucial in the pharmaceutical, dye, and pesticide industries. However, its theoretical description is extremely challenging, due to the associated long timescales ($ > 1 \, \mu s$). We…

Chemical Physics · Physics 2023-02-09 Oren Elishav , Roy Podgaetsky , Olga Meikler , Barak Hirshberg

The simulation of rare events is one of the key problems in atomistic simulations. Towards its solution a plethora of methods have been proposed. Here we combine two such methods metadynamics and inte-grated tempering sampling. In…

Chemical Physics · Physics 2018-10-29 Yi Isaac Yang , Haiyang Niu , Michele Parrinello

Performing alchemical transformations, in which one molecular system is nonphysically changed to another system, is a popular approach adopted in performing free energy calculations associated with various biophysical processes, such as…

Statistical Mechanics · Physics 2023-12-15 Wei-Tse Hsu , Valerio Piomponi , Pascal T. Merz , Giovanni Bussi , Michael R. Shirts

Designing an appropriate set of collective variables is crucial to the success of several enhanced sampling methods. Here we focus on how to obtain such variables from information limited to the metastable states. We characterize these…

Chemical Physics · Physics 2020-04-08 Luigi Bonati , Valerio Rizzi , Michele Parrinello

We investigate the role of stochastic resetting in non-Markovian systems, where memory effects arise due to slow relaxation, rugged energy landscapes, disordered environments, and molecular crowding. Using the celebrated continuous-time…

Statistical Mechanics · Physics 2026-04-13 Suvam Pal , Rahul Das , Arnab Pal