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Sampling complex free energy surfaces is one of the main challenges of modern atomistic simulation methods. The presence of kinetic bottlenecks in such surfaces often renders a direct approach useless. A popular strategy is to identify a…

Computational Physics · Physics 2019-09-25 Luigi Bonati , Yue-Yu Zhang , Michele Parrinello

Free energies as a function of a selected set of collective variables are commonly computed in molecular simulation and of significant value in understanding and engineering molecular behavior. These free energy surfaces are most commonly…

Statistical Mechanics · Physics 2022-11-15 Michael R. Shirts , Andrew L. Ferguson

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

Biased sampling of collective variables is widely used to accelerate rare events in molecular simulations and to explore free energy surfaces. However, computational efficiency of these methods decreases with increasing number of collective…

Chemical Physics · Physics 2017-04-05 Shalini Awasthi , Nisanth N. Nair

A new simulated tempering method, which is referred to as simulated tempering umbrella sampling, for calculating the free energy of chemical reactions is proposed. First principles molecular dynamics simulations with this simulated…

Statistical Mechanics · Physics 2012-06-05 Yoshiharu Mori , Yuko Okamoto

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

The Collective Variables Dashboard is a software tool for real-time, seamless exploration of molecular structures and trajectories in a customizable space of collective variables. The Dashboard arises from the integration of the Collective…

Computational Physics · Physics 2022-02-21 Jérôme Hénin , Laura J. S. Lopes , Giacomo Fiorin

The principles behind the computation of protein-ligand binding free energies by Monte Carlo integration are described in detail. The simulation provides gas-phase binding free energies that can be converted to aqueous energies by solvation…

Chemical Physics · Physics 2017-01-25 Matthew Clark , Jeffrey S. Wiseman

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

Molecular dynamics is a powerful tool for studying the thermodynamics and kinetics of complex molecular events. However, these simulations can rarely sample the required time scales in practice. Transition path sampling overcomes this…

Chemical Physics · Physics 2023-07-31 Gianmarco Lazzeri , Hendrik Jung , Peter G. Bolhuis , Roberto Covino

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

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

We present a molecular simulation method to simultaneously find multiple transition pathways, and their associated free-energy profiles. The scheme extends path-metadynamics (PMD) [Phys. Rev. Lett. 109, 020601 (2012)] with multiple paths…

Statistical Mechanics · Physics 2025-06-23 Alberto Pérez de Alba Ortíz , Bernd Ensing

In particle physics, as in many areas of science, parameter inference relies on simulations to bridge the gap between theory and experiment. Recent developments in simulation-based inference have boosted the sensitivity of analyses;…

High Energy Physics - Phenomenology · Physics 2026-04-23 Ezequiel Alvarez , Sean Benevedes , Manuel Szewc , Jesse Thaler

We address the problem of constructing accurate mathematical models of the dynamics of molecular systems projected on a collective variable. To this aim we introduce an algorithm optimizing the parameters of a standard or generalized…

Statistical Mechanics · Physics 2018-10-02 Andrea Pérez-Villa , Fabio Pietrucci

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

An approach for incorporating embedded simulation and analysis capabilities in complex simulation codes through template-based generic programming is presented. This approach relies on templating and operator overloading within the C++…

Mathematical Software · Computer Science 2012-05-17 Roger P. Pawlowski , Eric T. Phipps , Andrew G. Salinger

Accurate phase diagram calculation from molecular dynamics requires systematic treatment and convergence of statistical averages. In this work we propose a Gaussian process regression based framework for reconstructing the free energy…

Computational Physics · Physics 2021-11-02 V. Ladygin , I. Beniya , E. Makarov , A. Shapeev

A family of fast sampling methods is introduced here for molecular simulations of systems having rugged free energy landscapes. The methods represent a generalization of a strategy consisting of adjusting a model for the free energy as a…

Computational Physics · Physics 2022-02-07 Pablo F. Zubieta Rico , Juan J. de Pablo

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