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Extracting consistent statistics between relevant free-energy minima of a molecular system is essential for physics, chemistry and biology. Molecular dynamics (MD) simulations can aid in this task but are computationally expensive,…

Chemical Physics · Physics 2024-04-17 Ana Molina-Taborda , Pilar Cossio , Olga Lopez-Acevedo , Marylou Gabrié

Accurate force fields are essential for reliable molecular simulations. These models are refined against quantum mechanical calculations and experimental measurements, which are subject to random and systematic errors. Bayesian Inference of…

Chemical Physics · Physics 2025-11-04 Robert M. Raddi , Vincent A. Voelz

We present a method to obtain numerically accurate values of configurational free energies of semiflexible macromolecular systems, based on the technique of thermodynamic integration combined with normal-mode analysis of a reference system…

Biomolecules · Quantitative Biology 2018-10-17 Stefan M. Giovan , Robert G. Scharein , Andreas Hanke , Stephen D. Levene

Free energy perturbation (FEP) is frequently used to evaluate the free energy change of a biological process, e.g. the drug binding free energy or the ligand solvation free energy. Due to the sampling inefficiency, FEP is often employed…

Chemical Physics · Physics 2017-01-31 Ying-Chih Chiang , Frank Otto

Relative Binding Free Energy (RBFE) calculations are a cornerstone of rational hit-to-lead and lead optimization in modern drug discovery. However, the high computational cost and limited reliability in tackling large or complex molecular…

Chemical Physics · Physics 2026-05-13 Narjes Ansari , Félix Aviat , Jérôme Hénin , Jean-Philip Piquemal , Louis Lagardère

In this work, I propose a statistical mechanical framework, for the evaluation of the free energy in molecular systems, by "deleting" all the molecules in a "single" step. The approach can be considered as the statistical mechanics…

Statistical Mechanics · Physics 2011-08-16 Georgios C. Boulougouris

We present an ab initio approach for evaluating a free energy profile along a reaction coordinate by combining logarithmic mean force dynamics (LogMFD) and first-principles molecular dynamics. The mean force, which is the derivative of the…

Chemical Physics · Physics 2014-05-29 Makoto Nakamura , Masao Obata , Tetsuya Morishita , Tatsuki Oda

We have developed a thorough and accurate method of determining anharmonic free energies, the temperature dependent effective potential technique (TDEP). It is based on \emph{ab initio} molecular dynamics followed by a mapping onto a model…

Statistical Mechanics · Physics 2013-10-14 Olle Hellman , Peter Steneteg , Igor A. Abrikosov , Sergei I. Simak

Many methods to accelerate sampling of molecular configurations are based on the idea that temperature can be used to accelerate rare transitions. These methods typically compute equilibrium properties at a target temperature using…

Chemical Physics · Physics 2023-11-30 Kangxin Liu , Grant M. Rotskoff , Eric Vanden-Eijnden , Glen M. Hocky

In adaptive-bias enhanced sampling methods, a bias potential is added to the system to drive transitions between metastable states. The bias potential is a function of a few collective variables and is gradually modified according to the…

Computational Physics · Physics 2022-05-30 Michele Invernizzi , Michele Parrinello

Large-scale atomistic simulations rely on interatomic potentials providing an efficient representation of atomic energies and forces. Modern machine-learning (ML) potentials provide the most precise representation compared to electronic…

Computational Physics · Physics 2025-04-23 David Immel , Ralf Drautz , Godehard Sutmann

We present a new method that combines alchemical transformation with physical pathway to accurately and efficiently compute the absolute binding free energy of receptor-ligand complex. Currently, the double decoupling method (DDM) and the…

Biomolecules · Quantitative Biology 2018-08-29 Nanjie Deng , Lauren Wickstrom , Emilio Gallicchio

This paper introduces a method for computing the Helmholtz free energy using the flow matching technique. Unlike previous work that utilized flow-based models for variational free energy calculations, this method provides bounds for free…

Computational Physics · Physics 2025-01-03 Lu Zhao , Lei Wang

Pre-calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via "library-based Monte Carlo") and for obtaining absolute free energies using a polymer-growth formalism.…

Quantitative Methods · Quantitative Biology 2018-12-26 Steven Lettieri , Artem B. Mamonov , Daniel M. Zuckerman

This paper develops and analyzes a stochastic derivative-free optimization strategy. A key feature is the state-dependent adaptive variance. We prove global convergence in probability with algebraic rate and give the quantitative results in…

Optimization and Control · Mathematics 2023-02-10 Björn Engquist , Kui Ren , Yunan Yang

This work reports an efficient density-fitting implementation of the density-based basis-set correction (DBBSC) method in the MOLPRO software. This method consists in correcting the energy calculated by a wave-function method with a given…

We introduce a simple enhanced sampling approach for the calculation of free energy differences and barriers along a one-dimensional reaction coordinate. First, a small number of short nonequilibrium simulations are carried out along the…

Chemical Physics · Physics 2021-11-03 Kristof M. Bal

Free energy calculations in molecular simulations have a variety of applications including determining the strength of molecular processes such as solvation and binding. It has been recently shown that when removing the VDW and Coulomb…

Chemical Physics · Physics 2015-07-15 Asaf Farhi , Bipin Singh

We present a detailed comparison of computational efficiency and precision for several free energy difference ($\Delta F$) methods. The analysis includes both equilibrium and non-equilibrium approaches, and distinguishes between…

Biological Physics · Physics 2009-11-11 F. Marty Ytreberg , Robert H. Swendsen , Daniel M. Zuckerman

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