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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

RNA function is intimately related to its structural dynamics. Molecular dynamics simulations are useful for exploring biomolecular flexibility but are severely limited by the accessible timescale. Enhanced sampling methods allow this…

Biomolecules · Quantitative Biology 2018-02-06 Vojtěch Mlýnský , Giovanni Bussi

Molecular dynamics (MD) enables the study of physical systems with excellent spatiotemporal resolution but suffers from severe time-scale limitations. To address this, enhanced sampling methods have been developed to improve exploration of…

Statistical Mechanics · Physics 2023-06-19 Shams Mehdi , Zachary Smith , Lukas Herron , Ziyue Zou , Pratyush Tiwary

Molecular dynamics simulations are widely used across chemistry, physics, and biology, providing quantitative insight into complex processes with atomic detail. However, their limited timescale of a few microseconds is a significant…

Chemical Physics · Physics 2025-04-10 Ofir Blumer , Barak Hirshberg

Molecular Dynamics (MD) simulations are fundamental computational tools for the study of proteins and their free energy landscapes. However, sampling protein conformational changes through MD simulations is challenging due to the relatively…

Biomolecules · Quantitative Biology 2023-07-20 Diego E. Kleiman , Hassan Nadeem , Diwakar Shukla

Molecular dynamics simulations have become essential in many areas of atomistic modelling from drug discovery to materials science. They provide critical atomic-level insights into key dynamical events experiments cannot easily capture.…

Biological Physics · Physics 2024-06-14 Tiejun Wei , Balint Dudas , Edina Rosta

Many processes in chemistry and physics take place on timescales that cannot be explored using standard molecular dynamics simulations. This renders the use of enhanced sampling mandatory. Here we introduce an enhanced sampling method that…

Chemical Physics · Physics 2020-06-12 Jayashrita Debnath , Michele Parrinello

Molecular simulations are playing an ever increasing role, finding applications in fields as varied as physics, chemistry, biology and material science. However, many phenomena of interest take place on time scales that are out of reach of…

Computational Physics · Physics 2021-10-07 Michele Invernizzi

We present a method for enhanced sampling of molecular dynamics simulations using stochastic resetting. Various phenomena, ranging from crystal nucleation to protein folding, occur on timescales that are unreachable in standard simulations.…

Chemical Physics · Physics 2023-02-09 Ofir Blumer , Shlomi Reuveni , Barak Hirshberg

This review article discusses some common enhanced sampling methods in relation to the process of self-assembly of biomolecules. An introduction to self-assembly and its challenges is covered followed by a brief overview of the methods and…

Soft Condensed Matter · Physics 2025-03-03 Mason Hooten , Het Patel , Yiwei Shao , Rishabh Kumar Singh , Meenakshi Dutt

This review describes recent advances by the authors and others on the topic of incorporating experimental data into molecular simulations through maximum entropy methods. Methods which incorporate experimental data improve accuracy in…

Chemical Physics · Physics 2019-05-15 Dilnoza B. Amirkulova , Andrew D. White

We introduce dynamic nested sampling: a generalisation of the nested sampling algorithm in which the number of "live points" varies to allocate samples more efficiently. In empirical tests the new method significantly improves calculation…

Computation · Statistics 2019-08-27 Edward Higson , Will Handley , Mike Hobson , Anthony Lasenby

Molecular simulations and biophysical experiments can be used to provide independent and complementary insights into the molecular origin of biological processes. A particularly useful strategy is to use molecular simulations as a modelling…

Chemical Physics · Physics 2019-12-10 Simone Orioli , Andreas Haahr Larsen , Sandro Bottaro , Kresten Lindorff-Larsen

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

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

In biomolecular systems (especially all-atom models) with many degrees of freedom such as proteins and nucleic acids, there exist an astronomically large number of local-minimum-energy states. Conventional simulations in the canonical…

Statistical Mechanics · Physics 2010-12-30 Ayori Mitsutake , Yoshiharu Mori , Yuko Okamoto

Equilibrium sampling of biomolecules remains an unmet challenge after more than 30 years of atomistic simulation. Efforts to enhance sampling capability, which are reviewed here, range from the development of new algorithms to…

Biomolecules · Quantitative Biology 2010-09-16 Daniel M. Zuckerman

Experiment directed simulation is a technique to minimally bias molecular dynamics simulations to match experimentally observed results. The method improves accuracy but does not address the sampling problem of molecular dynamics…

Chemical Physics · Physics 2019-02-07 Dilnoza B Amirkulova , Andrew D White

Molecular dynamics (MD) has become a powerful tool for studying biophysical systems, due to increasing computational power and availability of software. Although MD has made many contributions to better understanding these complex…

Computational Physics · Physics 2019-09-27 Yihang Wang , Joao Marcelo Lamim Ribeiro , Pratyush Tiwary

Normal molecular dynamics simulations are usually unable to simulate chemical reactions due to the low probability of forming the transition state. Therefore, enhanced sampling methods are implemented to accelerate the occurrence of…

Chemical Physics · Physics 2022-10-14 Yi Sun , Xu Han , Lijiang Yang
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