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Umbrella sampling is an efficient method for the calculation of free energy changes of a system along well-defined reaction coordinates. However, when multiple parallel channels along the reaction coordinate or hidden barriers in directions…

Methodology · Statistics 2015-06-16 Mingjun Yang , Lijiang Yang , Yiqin Gao , Hao Hu

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

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

Because of growing interest in temperature-based sampling methods like replica exchange, this note aims to make some observations and raise some potentially important questions which we have not seen addressed sufficiently in the…

Biological Physics · Physics 2007-05-23 Daniel M. Zuckerman , Edward Lyman

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

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 study the dynamics of parallel tempering simulations, also known as the replica exchange technique, which has become the method of choice for simulation of proteins and other complex systems. Recent results for the optimal choice of the…

Statistical Mechanics · Physics 2009-11-13 Walter Nadler , Ulrich H. E. Hansmann

In the replica-exchange molecular dynamics method, where constant-temperature molecular dynamics simulations are performed in each replica, one usually rescales the momentum of each particle after replica exchange. This rescaling method had…

Statistical Mechanics · Physics 2010-04-14 Yoshiharu Mori , Yuko Okamoto

In this short note we sketch the statistical physics framework of the replica exchange technique when applied to molecular dynamics simulations. In particular, we draw attention to generalized move sets that allow a variety of optimizations…

Quantitative Methods · Quantitative Biology 2009-11-13 Walter Nadler , Ulrich H. E. Hansmann

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 discuss multi-dimensional generalizations of multicanonical algorithm, simulated tempering, and replica-exchange method. We generalize the original potential energy function $E_0$ by adding any physical quantity $V$ of interest as a new…

Statistical Mechanics · Physics 2008-10-08 Ayori Mitsutake , Yuko Okamoto

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

Designing an appropriate set of collective variables is crucial to the success of several enhanced sampling methods. Here we focus on how to obtain such variables from information limited to the metastable states. We characterize these…

Chemical Physics · Physics 2020-04-08 Luigi Bonati , Valerio Rizzi , 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

Replica exchange molecular dynamics (REMD) becomes more efficient as the frequency of swap between the temperatures is increased. Recently in [Plattner et al, J. Chem. Phys. 135, 134111 (2011)] a method was proposed to implement infinite…

Statistical Mechanics · Physics 2015-06-12 Jianfeng Lu , Eric Vanden-Eijnden

Fast and accurate sampling method is in high demand, in order to bridge the large gaps between molecular dynamic simulations and experimental observations. Recently, integrated tempering enhanced sampling method (ITS) has been proposed and…

Numerical Analysis · Mathematics 2018-06-22 Zhiyi You , Liying Li , Jianfeng Lu , Hao Ge

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

In adaptive-bias enhanced sampling methods, a bias potential is added to the system to drive transitions between metastable states. The bias potential is a function of a few collective variables and is gradually modified according to the…

Computational Physics · Physics 2022-05-30 Michele Invernizzi , Michele Parrinello

We introduce the well-tempered ensemble (WTE) which is the biased ensemble sampled by well-tempered metadynamics when the energy is used as collective variable. WTE can be designed so as to have approximately the same average energy as the…

Statistical Mechanics · Physics 2015-05-14 M. Bonomi , M. Parrinello

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