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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

The proper choice of collective variables (CVs) is central to biased-sampling free energy reconstruction methods in molecular dynamics simulations. The PLUMED 2 library, for instance, provides several sophisticated CV choices, implemented…

Computational Physics · Physics 2018-02-28 Toni Giorgino

Collective variables (CVs) are low-dimensional projections of high-dimensional system states. They are used to gain insights into complex emergent dynamical behaviors of processes on networks. The relation between CVs and network measures…

Physics and Society · Physics 2026-03-19 Marvin Lücke , Stefanie Winkelmann , Jobst Heitzig , Nora Molkenthin , Péter Koltai

The sampling problem lies at the heart of atomistic simulations and over the years many different enhanced sampling methods have been suggested towards its solution. These methods are often grouped into two broad families. On the one hand…

Computational Physics · Physics 2020-11-25 Michele Invernizzi , Pablo Miguel Piaggi , Michele Parrinello

Understanding the long-time dynamics of complex physical processes depends on our ability to recognize patterns. To simplify the description of these processes, we often introduce a set of reaction coordinates, customarily referred to as…

Chemical Physics · Physics 2024-12-31 Tuğçe Gökdemir , Jakub Rydzewski

High-dimensional metastable molecular system can often be characterised by a few features of the system, i.e. collective variables (CVs). Thanks to the rapid advance in the area of machine learning and deep learning, various deep…

Machine Learning · Computer Science 2023-08-10 Wei Zhang , Christof Schütte

Rare event sampling is a central problem in modern computational chemistry research. Among the existing methods, transition path sampling (TPS) can generate unbiased representations of reaction processes. However, its efficiency depends on…

Computational Physics · Physics 2024-04-04 Jintu Zhang , Odin Zhang , Luigi Bonati , TingJun Hou

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

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

Biased enhanced sampling methods utilizing collective variables (CVs) are powerful tools for sampling conformational ensembles. Due to high intrinsic dimensions, efficiently generating conformational ensembles for complex systems requires…

Machine Learning · Computer Science 2023-12-19 Yikai Liu , Tushar K. Ghosh , Guang Lin , Ming Chen

A popular way to accelerate the sampling of rare events in molecular dynamics simulations is to introduce a potential that increases the fluctuations of selected collective variables. For this strategy to be successful, it is critical to…

Computational Physics · Physics 2021-01-19 Luigi Bonati

Enhanced sampling algorithms have emerged as powerful methods to extend the utility of molecular dynamics simulations and allow the sampling of larger portions of the configuration space of complex systems in a given amount of simulation…

Statistical Mechanics · Physics 2022-12-19 Jérôme Hénin , Tony Lelièvre , Michael R. Shirts , Omar Valsson , Lucie Delemotte

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

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

Molecular dynamics is crucial for understanding molecular systems but its applicability is often limited by the vast timescales of rare events like protein folding. Enhanced sampling techniques overcome this by accelerating the simulation…

Machine Learning · Computer Science 2026-02-24 Seonghyun Park , Kiyoung Seong , Soojung Yang , Rafael Gómez-Bombarelli , Sungsoo Ahn

We introduce a novel enhanced sampling approach named OPES flooding for calculating the kinetics of rare events from atomistic molecular dynamics simulation. This method is derived from the On-the-fly-Probability-Enhanced-Sampling (OPES)…

Chemical Physics · Physics 2022-10-31 Dhiman Ray , Narjes Ansari , Valerio Rizzi , Michele Invernizzi , Michele Parrinello

Diffusion-based samplers learn to sample complex, high-dimensional distributions using energies or log densities alone, without training data. Yet, they remain impractical for molecular sampling because they are often slower than molecular…

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

We propose two approaches for selecting variables in latent class analysis (i.e.,mixture model assuming within component independence), which is the common model-based clustering method for mixed data. The first approach consists in…

Computation · Statistics 2017-03-08 Matthieu Marbac , Mohammed Sedki

Developing an efficient method to accelerate the speed of molecular dynamics is a central theme in the field of molecular simulation. One category among the methods are collective-variable-based methods, which rely on predefined collective…

Chemical Physics · Physics 2024-08-27 Jiahao Fan , Yanze Wang , Dongdong Wang , Linfeng Zhang