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Free energy calculations based on atomistic Hamiltonians provide microscopic insight into the thermodynamic driving forces of biophysical or condensed matter systems. Many approaches use intermediate Hamiltonians interpolating between the…

Computational Physics · Physics 2021-12-08 Martin Reinhardt , Helmut Grubmüller

We present a new method to evaluate vibrational free energies of atomic systems without a priori specification of an interatomic potential. Our model-agnostic approach leverages descriptors, high-dimensional feature vectors of atomic…

Materials Science · Physics 2025-03-05 Thomas D Swinburne , Clovis Lapointe , Mihai-Cosmin Marinica

A new method for calculating the total energy of Si systems is presented. The method is based on the effective-medium theory concept of a reference system. Instead of calculating the energy of an atom in the system of interest a reference…

Condensed Matter · Physics 2016-08-14 K. Stokbro , N. Chetty , K. W. Jacobsen , J. K. Nørskov

In randomized dose-finding trials, although drug exposure data form a part of key information for dose selection, the evaluation of the dose-response (DR) relationship often mainly uses DR data. We examine the benefit of…

Methodology · Statistics 2025-08-07 Jixian Wang , Zhiwei Zhang , Ram Tiwari

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

Sets of free energy differences are useful for finding the equilibria of chemical reactions, while absolute free energies have little physical meaning. However finding the relative free energy between two macrostates by subtraction of their…

Statistical Mechanics · Physics 2012-11-26 Joshua T. Berryman , Tanja Schilling

Accurate prediction of binding free energies is critical to streamlining the drug development and protein design process. With the advent of GPU acceleration, absolute alchemical methods, which simulate the removal of ligand electrostatics…

Biological Physics · Physics 2021-03-17 Edward King , Ruxi Qi , Han Li , Ray Luo , Erick Aitchison

We consider $N$ bosons in a box in $\mathbb {R}^d$ with volume $N/\rho$ under the influence of a mutually repellent pair potential. The particle density $\rho\in (0,\infty)$ is kept fixed. Our main result is the identification of the…

Probability · Mathematics 2011-04-20 Stefan Adams , Andrea Collevecchio , Wolfgang König

We have obtained the binding energy of the deuteron on a quantum simulator using the variational quantum eigensolver for renormalization group (RG)-based low-momentum effective interactions. The binding energy (BE) has been calculated in…

Nuclear Theory · Physics 2026-05-27 Sreelekshmi Pillai , S. Ramanan , V. Balakrishnan , S. Lakshmibala

We present receptor hopping and receptor swapping free energy estimation protocols based on the Alchemical Transfer Method (ATM) to model the binding selectivity of a set of ligands to two arbitrary receptors. The receptor hopping protocol,…

Chemical Physics · Physics 2024-08-28 Solmaz Azimi , Emilio Gallicchio

We present an approximate method for calculating the electrostatic free energy of concentrated protein solutions. Our method uses a cell model and accounts for both the coulomb energy and the entropic cost of Donnan salt partitioning. The…

Biological Physics · Physics 2013-04-10 Shradha Mishra , Jeremy D. Schmit

The efficacy of drug treatments depends on how tightly small molecules bind to their target proteins. The rapid and accurate quantification of the strength of these interactions (as measured by binding affinity) is a grand challenge of…

Distributed, Parallel, and Cluster Computing · Computer Science 2018-10-30 Jumana Dakka , Kristof Farkas-Pall , Matteo Turilli , David W Wright , Peter V Coveney , Shantenu Jha

Free energies govern the behavior of soft and liquid matter, and improving their predictions could have a large impact on the development of drugs, electrolytes or homogeneous catalysts. Unfortunately, it is challenging to devise an…

Chemical Physics · Physics 2021-04-14 Jan Weinreich , Nicholas J. Browning , O. Anatole von Lilienfeld

The hydration free energies of ions exhibit an approximately quadratic dependence on the ionic charge, as predicted by the Born model. We analyze this behavior using second-order perturbation theory. This provides effective methods to…

chem-ph · Physics 2008-02-03 Gerhard Hummer , Lawrence R. Pratt , Angel E. Garcia

In this study, we carried out equilibrium molecular dynamics (EMD) simulations of the liquid-liquid interface between two different Lennard-Jones components with varying miscibility, where we examined the relation between the interfacial…

Soft Condensed Matter · Physics 2025-12-29 Rei Ogawa , Hiroki Kusudo , Takeshi Omori , Edward R. Smith , Laurent Joly , Samy Merabia , Yasutaka Yamaguchi

The theory behind computation of absolute binding free energies using explicit-solvent molecular simulations is well-established, yet somewhat complex, with counter-intuitive aspects. This leads to frequent frustration, common…

Chemical Physics · Physics 2021-05-26 Elise Duboué-Dijon , Jérôme Hénin

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

The accurate prediction of protein-ligand binding affinities is crucial for drug discovery. Alchemical free energy calculations have become a popular tool for this purpose. However, the accuracy and reliability of these methods can vary…

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

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