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Calculating free energy differences is a topic of substantial interest and has many applications including molecular docking and hydration, solvation, and binding free energies which is used in computational drug discovery. However, in…

Chemical Physics · Physics 2013-10-16 Asaf Farhi

In the present work, we present a hybrid quantum-classical workflow aimed at improving the accuracy of alchemical free energy (AFE) predictions by incorporating configuration interaction (CI) simulations using the book-ending correction…

Chemical Physics · Physics 2025-06-27 Milana Bazayeva , Zhen Li , Danil Kaliakin , Fangchun Liang , Akhil Shajan , Susanta Das , Kenneth M. Merz

Thermodynamic integration (TI) offers a rigorous method for estimating free-energy differences by integrating over a sequence of interpolating conformational ensembles. However, TI calculations are computationally expensive and typically…

Statistical Mechanics · Physics 2024-12-04 Bálint Máté , François Fleuret , Tristan Bereau

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

Mesh-free methods have significant potential for simulations in complex geometries, as the time consuming process of mesh-generation is avoided. Smoothed Particle Hydrodynamics (SPH) is the most widely used mesh-free method, but suffers…

Computational Physics · Physics 2020-06-24 Jack King , Steven Lind , Abouzied Nasar

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…

Detailed chemistry-based computational fluid dynamics (CFD) simulations are computationally expensive due to the solution of the underlying chemical kinetics system of ordinary differential equations (ODEs). Here, we introduce a novel…

Nonadiabatic molecular dynamics (NAMD) is widely used to describe hot electron relaxation and nonradiative recombination processes, but high computational costs limit its application to large supercells. Here, we implement a nonadiabatic…

Chemical Physics · Physics 2026-05-26 Xiaoke He , Hsiao-Yi Tsai , Ziwei Chai , Junwen Yin , Zhongfei Xu , Li-Min Liu

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

Accurately predicting protein-ligand binding free energies (BFEs) remains a central challenge in drug discovery, particularly because the most reliable methods, such as free energy perturbation (FEP), are computationally intensive and…

Chemical Physics · Physics 2025-12-09 Farzad Molani , Art E. Cho

Alchemical free energy calculations are a useful tool for predicting free energy differences associated with the transfer of molecules from one environment to another. The hallmark of these methods is the use of "bridging" potential energy…

We present an efficient sampling method for computing a partition function and accelerating configuration sampling. The method performs a random walk in the $\lambda$ space, with $\lambda$ being any thermodynamic variable that characterizes…

Computational Physics · Physics 2010-03-02 Cheng Zhang , Jianpeng Ma

Performing alchemical transformations, in which one molecular system is nonphysically changed to another system, is a popular approach adopted in performing free energy calculations associated with various biophysical processes, such as…

Statistical Mechanics · Physics 2023-12-15 Wei-Tse Hsu , Valerio Piomponi , Pascal T. Merz , Giovanni Bussi , Michael R. Shirts

The massively parallel computation of absolute binding free energy with a well-equilibrated system (MP-CAFEE) has been developed [H. Fujitani, Y. Tanida, M. Ito, G. Jayachandran, C. D. Snow, M. R. Shirts, E. J. Sorin, and V. S. Pande, J.…

Soft Condensed Matter · Physics 2009-11-13 Yoshiaki Tanida , Masakatsu Ito , Hideaki Fujitani

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

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

Flow and diffusion models achieve high-fidelity, high-resolution image synthesis, but often require many function evaluations (NFEs) at sampling time. Existing acceleration methods either require additional training through distillation or…

Computer Vision and Pattern Recognition · Computer Science 2026-05-20 Anuska Roy , Pravin Nair

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

In this work, we present a general machine learning approach for full-dimensional potential energy surfaces for tetra-atomic systems. Our method employs an active learning scheme trained on {\it ab initio} points, which size grows based on…

Chemical Physics · Physics 2023-10-12 Xiangyue Liu , Weiqi Wang , Jesús Pérez-Ríos

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