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We develop a novel method of replica-exchange molecular dynamics (REMD) simulation, mass-scaling REMD (MSREMD) method, which improves trajectory accuracy at high temperatures, and thereby contributes to numerical stability. In addition, the…

Statistical Mechanics · Physics 2015-06-19 Tetsuro Nagai , Takuya Takahashi

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

The free energy landscapes of several fundamental processes are characterized by high barriers separating long-lived metastable states. In order to explore these type of landscapes enhanced sampling methods are used. While many such methods…

Chemical Physics · Physics 2019-04-12 Jayashrita Debnath , Michele Invernizzi , Michele Parrinello

The widespread popularity of replica exchange and expanded ensemble algorithms for simulating complex molecular systems in chemistry and biophysics has generated much interest in enhancing phase space mixing of these protocols, thus…

Statistical Mechanics · Physics 2011-12-06 John D. Chodera , Michael R. Shirts

We present a simulation protocol that allows for efficient sampling of the degrees of freedom of a solute in explicit solvent. The protocol involves using a non-equilibrium umbrella sampling method, in this case the recently developed…

Chemical Physics · Physics 2010-03-16 Volodymyr Babin , Celeste Sagui

Enhanced sampling techniques have become an essential tool in computational chemistry and physics, where they are applied to sample activated processes that occur on a time scale that is inaccessible to conventional simulations. Despite…

Chemical Physics · Physics 2022-01-13 F. Giberti , G. A. Tribello , M. Ceriotti

Metadynamics, a member of the `flat histogram' class of advanced sampling algorithms, has been widely used in molecular simulations to drive the exploration of states separated by high free energy barriers and promote comprehensive sampling…

Computational Physics · Physics 2021-09-13 Shanghui Huang , Michael J. Quevillon , Ernesto C. Cortés-Morales , Jonathan K. Whitmer

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

Hamiltonian Monte Carlo (HMC) is widely used for sampling from high dimensional target distributions with densities known up to proportionality. While HMC exhibits favorable scaling properties in high dimensions, it struggles with strongly…

Computation · Statistics 2025-07-30 Joonha Park

Atomistic modelling of phase transitions, chemical reactions, or other rare events that involve overcoming high free energy barriers usually entails prohibitively long simulation times. Introducing a bias potential as a function of an…

Computational Physics · Physics 2019-11-06 Federico Giberti , Bingqing Cheng , Gareth Aneurin Tribello , Michele Ceriotti

The simulation of rare events is one of the key problems in atomistic simulations. Towards its solution a plethora of methods have been proposed. Here we combine two such methods metadynamics and inte-grated tempering sampling. In…

Chemical Physics · Physics 2018-10-29 Yi Isaac Yang , Haiyang Niu , Michele Parrinello

Well-Tempered Metadynamics (WTmetaD) is an efficient method to enhance the reconstruction of the free-energy surface of proteins. WTmetaD guarantees a faster convergence in the long time limit in comparison with the standard metadynamics.…

Biological Physics · Physics 2015-06-12 Francois Sicard , Patrick Senet

The rare-event sampling problem has long been the central limiting factor in molecular dynamics (MD), especially in biomolecular simulation. Recently, diffusion models such as BioEmu have emerged as powerful equilibrium samplers that…

Subsampling is a widely used and effective approach for addressing the computational challenges posed by massive datasets. Substantial progress has been made in developing non-uniform, probability-based subsampling schemes that prioritize…

Methodology · Statistics 2026-05-07 Dingyi Wang , Haiying Wang , Qingpei Hu

Relative free energy calculations are now widely used in academia and industry, but the accuracy is often limited by poor sampling of the complexes conformational ensemble. To address this, we have developed a novel method termed…

Chemical Physics · Physics 2025-08-12 Anika J. Friedman , Wei-Tse Hsu , Michael R. Shirts

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

Conventional molecular-dynamics (cMD) simulation has a well-known limitation in accessible time and length scales, and thus various enhanced sampling techniques have been proposed to alleviate the problem. In this paper we explore the…

Chemical Physics · Physics 2018-01-17 Hadi H. Arefi , Takeshi Yamamoto

Many enhanced sampling methods, such as Umbrella Sampling, Metadynamics or Variationally Enhanced Sampling, rely on the identification of appropriate collective variables. For proteins, even small ones, finding appropriate collective…

Chemical Physics · Physics 2017-09-15 Ferruccio Palazzesi , Omar Valsson , Michele Parrinello

Molecular dynamics (MD) simulations are useful in obtaining thermodynamic and kinetic properties of bio-molecules but are limited by the timescale barrier, i.e., we may be unable to efficiently obtain properties because we need to run…

Chemical Physics · Physics 2017-08-23 Surl-Hee Ahn , Jay W. Grate , Eric F. Darve

Metadynamics is an established sampling method aimed at reconstructing the free-energy surface relative to a set of appropriately chosen collective variables. In standard metadynamics the free-energy surface is filled by the addition of…

Statistical Mechanics · Physics 2012-07-11 Davide Branduardi , Giovanni Bussi , Michele Parrinello