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Alchemical free energy calculations via molecular dynamics have been widely used to obtain thermodynamic properties related to protein-ligand binding and solute-solvent interactions. Although soft-core modeling is the most common approach,…

Computational Physics · Physics 2023-01-03 Gabriela B. Correa , Jessica C. S. L. Maciel , Frederico W. Tavares , Charlles R. A. Abreu

Free energies play a central role in characterising the behaviour of chemical systems and are among the most important quantities that can be calculated by molecular dynamics simulations. Solvation free energies in various organic solvents,…

Chemical Physics · Physics 2026-02-11 J. Harry Moore , Daniel J. Cole , Gabor Csanyi

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

Despite the modern level of development of computational chemistry methods and techno-logical progress, fast and accurate determination of solvation free energy remains a huge problem for physical chemists. In this paper, we describe two…

Chemical Physics · Physics 2021-05-18 N. N. Kalikin , Y. A. Budkov , A. L. Kolesnikov , D. V. Ivlev , M. A. Krestyaninov , M. G. Kiselev

An analytical description of polymer melts and their mixtures as liquids of interacting soft colloidal particles is obtained from liquid-state theory. The derived center-of-mass pair correlation functions with no adjustable parameters…

Soft Condensed Matter · Physics 2009-11-10 G. Yatsenko , E. J. Sambriski , M. A. Nemirovskaya , M. Guenza

Calculating relative free energies is a topic of substantial interest and has many applications including solvation and binding free energies, which are used in computational drug discovery. However, there remain the challenges of accuracy,…

Chemical Physics · Physics 2016-09-28 Asaf Farhi , Bipin Singh

The accurate prediction of solvation free energy is of significant importance as it governs the behavior of solutes in solution. In this work, we apply a variety of machine learning techniques to predict and analyze the alchemical free…

Chemical Physics · Physics 2024-11-11 Mingjun Han , Yukai Zhang , Taotao Yu , Guodong Du , ChiYung Yam , Ho-Kin Tang

The hydration or binding free energy of a drug-like molecule is a key data for early stage drug discovery. Hundreds of thousands of evaluations are needed, which rules out the exhaustive use of atomistic simulations and free energy methods.…

Chemical Physics · Physics 2018-06-11 Sohvi Luukkonen , Luc Belloni , Daniel Borgis , Maximilien Levesque

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

The hydration free energy of a macromolecule is the central property of interest for understanding its distribution over conformations and its state of aggregation. Calculating the hydration free energy of a macromolecule in all-atom…

Soft Condensed Matter · Physics 2022-06-22 Rohan S. Adhikari , Arjun Valiya Parambathu , Walter G. Chapman , Dilipkumar N. Asthagiri

We propose to relax geometries throughout chemical compound space (CCS) using alchemical perturbation density functional theory (APDFT). APDFT refers to perturbation theory involving changes in nuclear charges within approximate solutions…

Chemical Physics · Physics 2024-01-10 Giorgio Domenichini , O. Anatole von Lilienfeld

Classical density-functional theory is the most direct approach to equilibrium structures and free energies of inhomogeneous liquids, but requires the construction of an approximate free-energy functional for each liquid of interest. We…

Soft Condensed Matter · Physics 2014-10-10 Ravishankar Sundararaman , Kendra Letchworth-Weaver , T A Arias

We introduce an orbital free electron density functional approximation based on alchemical perturbation theory. Given convergent perturbations of a suitable reference system, the accuracy of popular self-consistent Kohn-Sham density…

Chemical Physics · Physics 2020-05-27 Guido Falk von Rudorff , O. Anatole von Lilienfeld

In transitions between different environmental settings, a molecular system inevitably undergoes a range of detectable changes, and the ability to accurately simulate such responses, e.g., in the form of shifts to molecular energies,…

Chemical Physics · Physics 2026-01-14 Kasper F. Schaltz , Jonas Greiner , Filippo Lipparini , Janus J. Eriksen

We present a method for computing free-energy differences using thermodynamic integration with a neural network potential that interpolates between two target Hamiltonians. The interpolation is defined at the sample distribution level, and…

Statistical Mechanics · Physics 2025-03-26 Bálint Máté , François Fleuret , Tristan Bereau

Solvation effect might have a tremendous influence on chemical reactions. However, precise quantum chemistry calculations are most often done either in vacuum neglecting the role of the solvent or using continuum solvent model ignoring its…

Chemical Physics · Physics 2020-07-14 Guillaume Jeanmairet , Maximilien Levesque , Daniel Borgis

We show that the energy of a perturbed system can be fully recovered from the unperturbed system's electron density. We derive an alchemical integral transform by parametrizing space in terms of transmutations, the chain rule and…

Chemical Physics · Physics 2022-10-28 Simon León Krug , Guido Falk von Rudorff , O. Anatole von Lilienfeld

We present an implementation of alchemical free energy simulations at the quantum mechanical level by directly interpolating the electronic Hamiltonian. The method is compatible with any level of electronic structure theory and requires…

Chemical Physics · Physics 2024-09-02 Chenghan Li , Xing Zhang , Garnet Kin-Lic Chan

Determining the solvation free energies of single ions in water is one of the most fundamental problems in physical chemistry and yet many unresolved questions remain. In particular, the ability to decompose the solvation free energy into…

Chemical Physics · Physics 2017-11-21 Timothy T. Duignan , Marcel D. Baer , Gregory K. Schenter , Christopher J. Mundy

In this work, the tetrahydrofuran (THF) hydrate-water interfacial free energy is determined at $500\,\text{bar}$, at one point of the univariant two-phase coexistence line of the THF hydrate, by molecular dynamics simulation. The Mold…

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