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We propose a formulation of adaptive computation of free energy differences, in the ABF or nonequilibrium metadynamics spirit, using conditional distributions of samples of configurations which evolve in time. This allows to present a truly…

Statistical Mechanics · Physics 2015-06-25 Tony Lelievre , Mathias Rousset , Gabriel Stoltz

We propose an adiabatic reweighting algorithm for computing the free energy along an external parameter from adaptive molecular dynamics simulations. The adaptive bias is estimated using Bayes identity and information from all the sampled…

Statistical Mechanics · Physics 2014-04-08 Lingling Cao , Gabriel Stoltz , Tony Lelièvre , Mihai-Cosmin Marinica , Manuel Athènes

The ability of widely used sampling methods, such as molecular dynamics or Monte Carlo, to explore complex free energy landscapes is severely hampered by the presence of kinetic bottlenecks. A large number of solutions have been proposed to…

Statistical Mechanics · Physics 2014-08-29 Omar Valsson , 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

Existing adaptive bias techniques, which seek to estimate free energies and physical properties from molecular simulations, are limited by their reliance on fixed kernels or basis sets which hinder their ability to efficiently conform to…

Statistical Mechanics · Physics 2018-04-04 Hythem Sidky , Jonathan K. Whitmer

We propose an adaptive biasing algorithm aimed at enhancing the sampling of multimodal measures by Langevin dynamics. The underlying idea consists in generalizing the standard adaptive biasing force method commonly used in conjunction with…

Analysis of PDEs · Mathematics 2010-08-23 Chris Chipot , Tony Lelièvre

We develop an efficient sampling and free energy calculation technique within the adaptive biasing potential (ABP) framework. By mollifying the density of states we obtain an approximate free energy and an adaptive bias potential that is…

Statistical Mechanics · Physics 2010-01-29 Bradley M. Dickson , Frederic Legoll , Tony Lelievre , Gabriel Stoltz , Paul Fleurat-Lessard

Estimating the free energy in molecular simulation requires, implicitly or explicitly, counting how many times the system is observed in a finite region. If the simulation is biased by an external potential, the weight of the configurations…

Chemical Physics · Physics 2021-12-22 Matteo Carli , Alessandro Laio

Free energy landscapes encode the kinetics, intermediates, and transition states that govern molecular processes and are thus a key target of single biomolecule research. Typical approaches to deriving optimal, error-minimizing,…

Biological Physics · Physics 2025-11-25 Oliver Cheng , Zosia Adamska , Michael P. Brenner , Megan C. Engel

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

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

We propose a proof of convergence of an adaptive method used in molecular dynamics to compute free energy profiles. Mathematically, it amounts to studying the long-time behavior of a stochastic process which satisfies a non-linear…

Analysis of PDEs · Mathematics 2007-06-13 Tony Lelievre , Felix Otto , Mathias Rousset , Gabriel Stoltz

Free-energy-based adaptive biasing methods, such as Metadynamics, the Adaptive Biasing Force (ABF) and their variants, are enhanced sampling algorithms widely used in molecular simulations. Although their efficiency has been empirically…

Probability · Mathematics 2026-01-29 Tony Lelièvre , Xuyang Lin , Pierre Monmarché

Enhanced sampling and free energy calculation algorithms of the Thermodynamic Integration family (such as the Adaptive Biasing Force method, ABF) are not based on the direct computation of a free energy surface, but rather of its gradient.…

Computational Physics · Physics 2021-10-22 Jérôme Hénin

Many biological processes involve numerous coupled degrees of freedom, yet free-energy estimation is often restricted to one-dimensional profiles to mitigate the high computational cost of multidimensional sampling. In this work, we extend…

Statistical Mechanics · Physics 2026-02-12 Daniel Nagel , Tristan Bereau

We propose a new Monte Carlo algorithm for the free energy calculation based on configuration space sampling. We implement this algorithm for Ising model. Comparison with the exact free energy shows an excellent agreement. We analyse the…

Strongly Correlated Electrons · Physics 2015-08-05 Sheng Bi , Ning-Hua Tong

This paper is committed to investigate an extension of the classical adaptive biasing force method, which is used to compute the free energy related to the Boltzmann-Gibbs measure and a reaction coordinate function. The issue of this…

Probability · Mathematics 2017-11-08 Houssam AlRachid , Tony Lelievre

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

In this PhD thesis, we explore and apply methods inspired by the free energy principle to two important areas in machine learning and neuroscience. The free energy principle is a general mathematical theory of the necessary…

Artificial Intelligence · Computer Science 2021-08-31 Beren Millidge

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
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