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Free energy sampling methods allow studying the full dynamics of activated processes. Unfortunately, the affordable accuracy of the potential describing the energy and forces of the system is usually rather low. Here we introduce a new…

Chemical Physics · Physics 2019-04-04 GiovanniMaria Piccini , Michele Parrinello

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

This article describes nonequilibrium techniques for the calculation of free energies of solids using molecular dynamics (MD) simulations. These methods provide an alternative to standard equilibrium thermodynamic integration methods and…

Materials Science · Physics 2022-01-13 Rodrigo Freitas , Mark Asta , Maurice de Koning

The Alchemical Transfer Method (ATM) is herein validated against the relative binding free energies of a diverse set of protein-ligand complexes. We employed a streamlined setup workflow, a bespoke force field, and the AToM-OpenMM software…

Chemical Physics · Physics 2023-08-21 Lieyang Chen , Yujie Wu , Chuanjie Wu , Ana Silveira , Woody Sherman , Huafeng Xu , Emilio Gallicchio

For classical discrete systems under constant composition typically refferred to substitutional alloys, we propose calculation method of Helmholtz free energy based on a set of special microscopic states. The advantage of the method is that…

Statistical Mechanics · Physics 2021-10-22 Ryogo Miyake , Subaru Sugie , Koretaka Yuge

In this contribution I critically revise the alchemical reversible approach in the context of the statistical mechanics theory of non covalent bonding in drug receptor systems. I show that most of the pitfalls and entanglements for the…

Biomolecules · Quantitative Biology 2016-06-29 Piero Procacci

Data scarcity, bias, and experimental noise are all frequently encountered problems in the application of deep learning to chemical and material science disciplines. Transfer learning has proven effective in compensating for the lack in…

Chemical Physics · Physics 2021-03-16 Florence H. Vermeire , William H. Green

Ensuring a satisfactory statistical convergence of anharmonic thermodynamic properties requires sampling of many atomic configurations, however the methods to obtain those necessarily produce correlated samples, thereby reducing the…

Statistical Mechanics · Physics 2022-06-07 Erki Metsanurk

We have developed a new simulation algorithm for free-energy calculations. The method is a multidimensional extension of the replica-exchange method. While pairs of replicas with different temperatures are exchanged during the simulation in…

Statistical Mechanics · Physics 2009-10-31 Yuji Sugita , Akio Kitao , Yuko Okamoto

Fast and accurate evaluation of free energy has broad applications from drug design to material engineering. Computing the absolute free energy is of particular interest since it allows the assessment of the relative stability between…

Statistical Mechanics · Physics 2021-02-24 Xinqiang Ding , Bin Zhang

Gradients in free energies are the driving forces of physical and biochemical systems. To predict free energy differences with high accuracy, Molecular Dynamics (MD) and other methods based on atomistic Hamiltonians conduct sampling…

Computational Physics · Physics 2021-04-07 Martin Reinhardt , Helmut Grubmüller

Free energy calculation is critical in predictive tasks such as protein folding, docking and design. However, rigorous calculation of free energy change is prohibitively expensive in these practical applications. The minimum potential…

Biomolecules · Quantitative Biology 2016-03-08 Kai Wang , Lanru Liu , Pu Tian

We present a parameterized analytical model of alchemical molecular binding. The model describes accurately the free energy profiles of linear single-decoupling alchemical binding free energy calculations. The parameters of the model, which…

Biomolecules · Quantitative Biology 2017-07-06 Emilio Gallicchio

Quantum chemistry calculations such as the prediction of molecular properties and modeling of chemical reactions are a few of the critical areas where near-term quantum computers can showcase quantum advantage. We present a method to…

Quantum Physics · Physics 2022-04-06 Utkarsh Azad , Harjinder Singh

Predictions of relative stabilities of (competing) molecular crystals are of great technological relevance, most notably for the pharmaceutical industry. However, they present a long-standing challenge for modeling, as often minuscule free…

Materials Science · Physics 2022-05-25 Venkat Kapil , Edgar A Engel

Free energy calculations based on atomistic Hamiltonians and sampling are key to a first principles understanding of biomolecular processes, material properties, and macromolecular chemistry. Here, we generalize the Free Energy Perturbation…

Computational Physics · Physics 2023-07-19 Martin Reinhardt , Helmut Grubmüller

Predicting structural and energetic properties of a molecular system is one of the fundamental tasks in molecular simulations, and it has use cases in chemistry, biology, and medicine. In the past decade, the advent of machine learning…

Chemical Physics · Physics 2022-08-23 Sajjad Heydari , Stefano Raniolo , Lorenzo Livi , Vittorio Limongelli

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

This work addresses the question of whether it is possible to define simple pair-wise interaction terms to approximate free energies of proteins or polymers. Rather than ask how reliable a potential of mean force is, one can ask how…

Soft Condensed Matter · Physics 2009-10-31 Dirk Reith , Thomas Huber , Florian Mueller-Plathe , Andrew E. Torda

Thermodynamic phase transitions, a central concept in physics and chemistry, are typically controlled by an interplay of enthalpic and entropic contributions. In most cases, the estimation of the enthalpy in simulations is straightforward…

Soft Condensed Matter · Physics 2025-10-30 Yamin Ben-Shimon , Barak Hirshberg , Yohai Bar-Sinai