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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

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 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

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

We derived a number of numerical methods to treat biomolecular systems with multiple time scales. Based on the splitting of the operators associated with the slow-varying and fast-varying forces, new multiple time-stepping (MTS) methods are…

Numerical Analysis · Mathematics 2015-01-15 Chao Liang , Xiaolan Yuan , Xiantao Li

Metadynamics is a powerful method to accelerate molecular dynamics simulations, but its efficiency critically depends on the identification of collective variables that capture the slow modes of the process. Unfortunately, collective…

Chemical Physics · Physics 2023-07-17 Ofir Blumer , Shlomi Reuveni , Barak Hirshberg

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

Understanding kinetics and thermodynamics profile of biomolecules is necessary to understand their functional roles which has a major impact in mechanism driven drug discovery. Molecular dynamics simulation has been routinely used to…

Biomolecules · Quantitative Biology 2021-12-07 Soumendranath Bhakat

In ab initio molecular dynamics simulations of real-world problems, the simple Verlet method is still widely used for integrating the equations of motion, while more efficient algorithms are routinely used in classical molecular dynamics.…

Computational Physics · Physics 2016-08-03 Eiji Tsuchida

Many enhanced sampling techniques rely on the identification of a number of collective variables that describe all the slow modes of the system. By constructing a bias potential in this reduced space one is then able to sample efficiently…

Computational Physics · Physics 2019-03-05 Michele Invernizzi , Michele Parrinello

Many biological processes occur on time scales longer than those accessible to molecular dynamics simulations. Identifying collective variables (CVs) and introducing an external potential to accelerate them is a popular approach to address…

Computational Physics · Physics 2024-10-24 Enrico Trizio , Andrea Rizzi , Pablo M. Piaggi , Michele Invernizzi , Luigi Bonati

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

Many applications of computational fluid dynamics require multiple simulations of a flow under different input conditions. In this paper, a numerical algorithm is developed to efficiently determine a set of such simulations in which the…

Numerical Analysis · Mathematics 2017-05-29 Max Gunzburger , Nan Jiang , Zhu Wang

It is often difficult to quantitatively determine if a new molecular simulation algorithm or software properly implements sampling of the desired thermodynamic ensemble. We present some simple statistical analysis procedures to allow…

Statistical Mechanics · Physics 2013-03-04 Michael R. Shirts

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

A new self-learning algorithm for accelerated dynamics, reconnaissance metadynamics, is proposed that is able to work with a very large number of collective coordinates. Acceleration of the dynamics is achieved by constructing a bias…

Computational Physics · Physics 2010-10-15 Gareth A. Tribello , Michele Ceriotti , Michele Parrinello

This chapter discusses how the PLUMED plugin for molecular dynamics can be used to analyze and bias molecular dynamics trajectories. The chapter begins by introducing the notion of a collective variable and by then explaining how the free…

Computational Physics · Physics 2019-11-19 Giovanni Bussi , Gareth A. Tribello

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

Molecular dynamics is one of the most commonly used approaches for studying the dynamics and statistical distributions of many physical, chemical, and biological systems using atomistic or coarse-grained models. It is often the case,…

Computational Physics · Physics 2015-06-16 Ben Leimkuhler , Daniel T. Margul , Mark E. Tuckerman

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
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