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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

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

Metadynamics is an enhanced sampling method of great popularity, based on the on-the-fly construction of a bias potential that is function of a selected number of collective variables. We propose here a change in perspective that shifts the…

Computational Physics · Physics 2020-03-24 Michele Invernizzi , Michele Parrinello

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

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

In this paper we combine two powerful computational techniques, well-tempered metadynamics and time lagged independent component analysis. The aim is to develop a new tool for studying rare events and exploring complex free energy…

Statistical Mechanics · Physics 2017-12-08 James McCarty , Michele Parrinello

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

Sampling from discrete distributions with multiple modes and energy barriers is fundamental to machine learning and computational physics. Recent discrete neural samplers like MDNS suffer from mode collapse and fail to sample high-energy…

We present a unique derivation of metadynamics. The starting point for the derivation is an on-the-fly reweighting scheme but through an approximation we recover the standard metadynamics and the well-tempered metadynamics in a general form…

Statistical Mechanics · Physics 2011-11-10 Bradley M. Dickson

The computational study of conformational transitions in RNA and proteins with atomistic molecular dynamics often requires suitable enhanced sampling techniques. We here introduce a novel method where concurrent metadynamics are integrated…

Computational Physics · Physics 2015-09-01 Alejandro Gil-Ley , Giovanni Bussi

Stochastic systems often exhibit multiple viable metastable states that are long-lived. Over very long timescales, fluctuations may push the system to transition between them, drastically changing its macroscopic configuration. In realistic…

Statistical Mechanics · Physics 2023-04-14 Tobias Grafke , Alessandro Laio

We present a method for determining the free energy dependence on a selected number of collective variables using an adaptive bias. The formalism provides a unified description which has metadynamics and canonical sampling as limiting…

Statistical Mechanics · Physics 2008-03-31 Alessandro Barducci , Giovanni Bussi , Michele Parrinello

Metadynamics (MTD) is a very powerful technique to sample high-dimensional free energy landscapes, and due to its self-guiding property, the method has been successful in studying complex reactions and conformational changes. MTD sampling…

Computational Physics · Physics 2016-02-05 Shalini Awasthi , Venkat Kapil , Nisanth N. Nair

Metasurfaces are ultrathin, engineered materials composed of nanostructures that manipulate light in ways unattainable by natural materials. Recent advances have leveraged computational optimization, machine learning, and deep learning to…

Optics · Physics 2025-08-08 Hao Li , Andrey Bogdanov

Metadynamics is a powerful computational tool to obtain the free energy landscape of complex systems. The Monte Carlo algorithm has proven useful to calculate thermodynamic quantities associated with simplified models of proteins, and thus…

Statistical Mechanics · Physics 2007-10-04 F. Marini , C. Camilloni , D. Provasi , R. A. Broglia , G. Tiana

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

This paper formalizes a widely used dynamical class--replicator-mutator dynamics and Price-style selection-and-transmission--and makes explicit the modeling choices (scale, atomic unit, interaction topology, transmission kernel) that…

Theoretical Economics · Economics 2026-01-13 Murad Farzulla

Sampling complex potential energies is one of the most pressing challenges of contemporary computational science. Inspired by recent efforts that use quantum effects and discretized Feynman's path integrals to overcome large barriers we…

Statistical Mechanics · Physics 2016-07-19 Marco Nava , Ferruccio Palazzesi , Claudio Perego , Michele Parrinello

The ability to predict accurate thermodynamic and kinetic properties in biomolecular systems is of both scientific and practical utility. While both remain very difficult, predictions of kinetics are particularly difficult because rates, in…

Chemical Physics · Physics 2018-06-13 Yong Wang , Omar Valsson , Pratyush Tiwary , Michele Parrinello , Kresten Lindorff-Larsen

Infrequent Metadynamics is a popular method to obtain the rates of long timescale processes from accelerated simulations. The inference procedure is based on rescaling the first-passage times of Metadynamics trajectories using a…

Chemical Physics · Physics 2025-03-04 Ofir Blumer , Shlomi Reuveni , Barak Hirshberg
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