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Metadynamics is a commonly used and successful enhanced sampling method. By the introduction of a history dependent bias which depends on a restricted number of collective variables(CVs) it can explore complex free energy surfaces…

Statistical Mechanics · Physics 2013-12-06 Pratyush Tiwary , Michele Parrinello

We introduce a method for elucidating and modifying the functionality of systems dominated by rare events that relies on the automated tuning of their underlying free energy surface. The proposed approach seeks to construct collective…

Computational Physics · Physics 2021-08-31 Dan Mendels , Juan J. de Pablo

We review two recently developed efficient methods for calculating rate constants of processes dominated by rare events in high-dimensional complex systems. The first is transition interface sampling (TIS), based on the measurement of…

Statistical Mechanics · Physics 2009-11-10 Titus S. van Erp , Peter G. Bolhuis

Enhanced sampling methods typically require predefined collective variables (CVs) that presuppose knowledge of reaction coordinates, restricting the discovery of unanticipated transition mechanisms or intermediates. Here, we show that a…

Chemical Physics · Physics 2026-04-08 Xiangrui Li , Daniel Schwalbe-Koda

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

The kinetics of collective rearrangements in solution, such as protein folding and nanocrystal phase transitions, often involve free energy barriers that are both long and rough. Applying methods of transition path sampling to harvest…

Statistical Mechanics · Physics 2009-11-13 M. Grünwald , P. L. Geissler , C. Dellago

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

We present a method to sample reactive pathways via biased molecular dynamics simulations in trajectory space. We show that the use of enhanced sampling techniques enables unconstrained exploration of multiple reaction routes. Time…

Computational Physics · Physics 2020-07-15 Davide Mandelli , Barak Hirshberg , Michele Parrinello

In modern day simulations of many-body systems much of the computational complexity is shifted to the identification of slowly changing molecular order parameters called collective variables (CV) or reaction coordinates. A vast array of…

Statistical Mechanics · Physics 2016-04-27 Pratyush Tiwary , B. J. Berne

Transition path sampling (TPS) is a powerful technique for investigating rare transitions, especially when the mechanism is unknown and one does not have access to the reaction coordinate. Straightforward application of TPS does not…

Chemical Physics · Physics 2019-07-11 Z. Faidon Brotzakis , Peter G. Bolhuis

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

Machine learning methods provide a general framework for automatically finding and representing the essential characteristics of simulation data. This task is particularly crucial in enhanced sampling simulations. There we seek a few…

Chemical Physics · Physics 2021-07-07 Jakub Rydzewski , Omar Valsson

Sampling complex free energy surfaces is one of the main challenges of modern atomistic simulation methods. The presence of kinetic bottlenecks in such surfaces often renders a direct approach useless. A popular strategy is to identify a…

Computational Physics · Physics 2019-09-25 Luigi Bonati , Yue-Yu Zhang , Michele Parrinello

Enhanced sampling simulations make the computational study of rare events feasible. A large family of such methods crucially depends on the definition of some collective variables (CVs) that could provide a low-dimensional representation of…

Computational Physics · Physics 2026-03-03 Jintu Zhang , Luigi Bonati , Enrico Trizio , Odin Zhang , Yu Kang , TingJun Hou , Michele Parrinello

Rare events such as conformational changes in biomolecules, phase transitions, and chemical reactions are central to the behavior of many physical systems, yet they are extremely difficult to study computationally because unbiased…

Machine Learning · Statistics 2026-04-16 Yuanqi Du , Jiajun He , Dinghuai Zhang , Eric Vanden-Eijnden , Carles Domingo-Enrich

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

Many recently introduced enhanced sampling techniques are based on biasing coarse descriptors (collective variables) of a molecular system on the fly. Sometimes the calculation of such collective variables is expensive and becomes a…

Computational Physics · Physics 2015-09-01 Marco Jacopo Ferrarotti , Sandro Bottaro , Andrea Pérez-Villa , Giovanni Bussi

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

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

Effective dynamics on a low-dimensional collective-variable (CV) or latent space can be simulated far more cheaply than the underlying high-dimensional stochastic system, but exploiting such coarse predictions requires lifting: turning a…

Dynamical Systems · Mathematics 2026-03-25 Christof Schütte , Alexander Sikorski , Jakob Kresse , Marcus Weber