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Identifying a reduced set of collective variables is critical for understanding atomistic simulations and accelerating them through enhanced sampling techniques. Recently, several methods have been proposed to learn these variables directly…

Computational Physics · Physics 2023-07-19 Luigi Bonati , Enrico Trizio , Andrea Rizzi , Michele Parrinello

Metadynamics is an enhanced sampling method of great popularity, based on the on-the-fly construction of a bias potential that is function of a selected number of collective variables. We propose here a change in perspective that shifts the…

Computational Physics · Physics 2020-03-24 Michele Invernizzi , Michele Parrinello

Protein function does not solely depend on structure but often relies on dynamical transitions between distinct conformations. Despite this fact, our ability to characterize or predict protein dynamics is substantially less developed…

Statistical Mechanics · Physics 2026-05-08 Michael A. Sauer , Souvik Mondal , Brandon Neff , Sthitadhi Maiti , Matthias Heyden

Biased sampling of collective variables is widely used to accelerate rare events in molecular simulations and to explore free energy surfaces. However, computational efficiency of these methods decreases with increasing number of collective…

Chemical Physics · Physics 2017-04-05 Shalini Awasthi , Nisanth N. Nair

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

Enhanced sampling methods are indispensable in computational physics and chemistry, where atomistic simulations cannot exhaustively sample the high-dimensional configuration space of dynamical systems due to the sampling problem. A class of…

Chemical Physics · Physics 2024-04-04 Jakub Rydzewski , Ming Chen , Tushar K. Ghosh , Omar Valsson

The adoption of detailed mechanisms for chemical kinetics often poses two types of severe challenges: First, the number of degrees of freedom is large; and second, the dynamics is characterized by widely disparate time scales. As a result,…

Dynamical Systems · Mathematics 2025-10-01 Eliodoro Chiavazzo , C. William Gear , Carmeline J. Dsilva , Neta Rabin , Ioannis G. Kevrekidis

Generating a data set that is representative of the accessible configuration space of a molecular system is crucial for the robustness of machine learned interatomic potentials (MLIP). However, the complexity of molecular systems,…

Machine Learning · Computer Science 2025-01-28 Aik Rui Tan , Johannes C. B. Dietschreit , Rafael Gomez-Bombarelli

Understanding protein conformational dynamics is essential for elucidating biological function but remains challenging due to the wide range of timescales and the complexity of collective motions. Enhanced sampling methods overcome…

Statistical Mechanics · Physics 2026-05-11 Souvik Mondal , Michael A. Sauer , Matthias Heyden

Many processes of scientific and technological interest are characterized by time scales that render their simulation impossible if one uses present day simulation capabilities. To overcome this challenge a variety of enhanced simulation…

Statistical Mechanics · Physics 2019-02-26 Z. Faidon Brotzakis , Dan Mendels , Michele Parrinello

In this work, we present Enhanced Representation-Based Sampling (ERBS), a novel enhanced sampling method designed to generate structurally diverse training datasets for machine-learned interatomic potentials. ERBS automatically identifies…

Chemical Physics · Physics 2026-01-23 Moritz René Schäfer , Johannes Kästner

While variable selection is essential to optimize the learning complexity by prioritizing features, automating the selection process is preferred since it requires laborious efforts with intensive analysis otherwise. However, it is not an…

Machine Learning · Computer Science 2019-10-29 Makiya Nakashima , Alex Sim , Youngsoo Kim , Jonghyun Kim , Jinoh Kim

Selection of appropriate collective variables for enhancing sampling of molecular simulations remains an unsolved problem in computational biophysics. In particular, picking initial collective variables (CVs) is particularly challenging in…

Machine Learning · Statistics 2018-05-15 Mohammad M. Sultan , Vijay S. Pande

We review a selection of methods for performing enhanced sampling in molecular dynamics simulations. We consider methods based on collective variable biasing and on tempering, and offer both historical and contemporary perspectives. In…

Statistical Mechanics · Physics 2014-01-03 Cameron Abrams , Giovanni Bussi

Collective variable (CV) or order parameter based enhanced sampling algorithms have achieved great success due to their ability to efficiently explore the rough potential energy landscapes of complex systems. However, the degeneracy of…

Chemical Physics · Physics 2018-07-11 Jing Zhang , Ming Chen

For many tasks of data analysis, we may only have the information of the explanatory variable and the evaluation of the response values are quite expensive. While it is impractical or too costly to obtain the responses of all units, a…

Computation · Statistics 2023-04-07 Wei Zheng , Ting Tian , Xueqin Wang

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

Molecular dynamics simulations hold great promise for providing insight into the microscopic behavior of complex molecular systems. However, their effectiveness is often constrained by long timescales associated with rare events. Enhanced…

Computational Physics · Physics 2026-03-03 Kai Zhu , Enrico Trizio , Jintu Zhang , Renling Hu , Linlong Jiang , Tingjun Hou , Luigi Bonati

We consider the problem of sampling a high dimensional multimodal target probability measure. We assume that a good proposal kernel to move only a subset of the degrees of freedoms (also known as collective variables) is known a priori.…

Statistical Mechanics · Physics 2025-02-07 Christoph Schönle , Marylou Gabrié , Tony Lelièvre , Gabriel Stoltz

We demonstrate how a prior assumption of smoothness can be used to enhance the reconstruction of free energy profiles from multiple umbrella sampling simulations using the Bayesian Gaussian process regression approach. The method we derive…

Statistical Mechanics · Physics 2014-07-25 Noam Bernstein , Thomas Stecher , Gábor Csányi