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Controlling polymorphism in molecular crystals is crucial in the pharmaceutical, dye, and pesticide industries. However, its theoretical description is extremely challenging, due to the associated long timescales ($ > 1 \, \mu s$). We…

Chemical Physics · Physics 2023-02-09 Oren Elishav , Roy Podgaetsky , Olga Meikler , Barak Hirshberg

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

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

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

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

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

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 phenomenon of solidification of a substance from its liquid phase is of the greatest practical and theoretical importance, and atomistic simulations can provide precious information towards its understanding and control. Unfortunately,…

Soft Condensed Matter · Physics 2021-03-25 Tarak Karmakar , Michele Invernizzi , Valerio Rizzi , Michele Parrinello

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

Enhanced sampling techniques such as umbrella sampling and metadynamics are now routinely used to provide information on how the thermodynamic potential, or free energy, depends on a small number of collective variables. The free energy…

Computational Physics · Physics 2018-08-31 Ilaria Gimondi , Gareth A. Tribello , Matteo Salvalaglio

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

Here we present a program aimed at free-energy calculations in molecular systems. It consists of a series of routines that can be interfaced with the most popular classical molecular dynamics (MD) codes through a simple patching procedure.…

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

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 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

A variety of enhanced sampling methods predict multidimensional free energy landscapes associated with biological and other molecular processes as a function of a few selected collective variables (CVs). The accuracy of these methods is…

Computational Physics · Physics 2024-04-09 Lukas Müllender , Andrea Rizzi , Michele Parrinello , Paolo Carloni , Davide Mandelli

Methods that combine collective variable (CV) based enhanced sampling and global tempering approaches are used in speeding-up the conformational sampling and free energy calculation of large and soft systems with a plethora of energy…

Computational Physics · Physics 2021-09-01 Anji Babu Kapakayala , Nisanth N. Nair

Identifying a reduced set of collective variables is critical for understanding atomistic simulations and accelerating them through enhanced sampling techniques. Recently, several methods have been proposed to learn these variables directly…

Computational Physics · Physics 2023-07-19 Luigi Bonati , Enrico Trizio , Andrea Rizzi , Michele Parrinello

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

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
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