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Predicting changes in binding free energy ($\Delta\Delta G$) is a vital task in protein engineering and protein-protein interaction (PPI) engineering for drug discovery. Previous works have observed a high correlation between $\Delta\Delta…

Machine Learning · Computer Science 2025-08-15 Patrick Soga , Zhenyu Lei , Yinhan He , Camille Bilodeau , Jundong Li

Free energy profiles serve as a fundamental bridge between microscopic atomic fluctuations and macroscopic thermodynamic observables. Estimating the free energy profile along a reaction coordinate, referred to as the potential of mean force…

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

Understanding how different classes of molecules move across biological membranes is a prerequisite to predicting a solute's permeation rate, which is a critical factor in the fields of drug design and pharmacology. We use biased Molecular…

Biological Physics · Physics 2018-05-16 Nihit Pokhrel , Lutz Maibaum

Advancements in AI for science unlocks capabilities for critical drug discovery tasks such as protein-ligand binding affinity prediction. However, current models overfit to existing oversimplified datasets that does not represent naturally…

Machine Learning · Computer Science 2025-12-02 Ming-Hsiu Wu , Ziqian Xie , Shuiwang Ji , Degui Zhi

Protein function does not solely depend on structure but often relies on dynamical transitions between distinct conformations. Despite this fact, our ability to characterize or predict protein dynamics is substantially less developed…

Statistical Mechanics · Physics 2026-05-08 Michael A. Sauer , Souvik Mondal , Brandon Neff , Sthitadhi Maiti , Matthias Heyden

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

The binomial acceptance correction procedure is studied for particle number distributions detected in high energy reactions in finite regions of the momentum space. We present acceptance correction formulas for scaled variance, skewness,…

High Energy Physics - Phenomenology · Physics 2020-03-25 Oleh Savchuk , Roman V. Poberezhnyuk , Volodymyr Vovchenko , Mark I. Gorenstein

In this work, an assessment of the CALPHAD method trained on only density functional theory (DFT) data is performed for the Li-Si binary system, as a case study. Using a parameter sampling approach based on the Bayesian Error Estimation…

Materials Science · Physics 2020-03-31 Ying Yuan , Gregory Houchins , Pin-Wen Guan , Venkatasubramanian Viswanathan

Computationally-guided material discovery is being increasingly employed using a descriptor-based screening through the calculation of a few properties of interest. A precise understanding of the uncertainty associated with first principles…

Materials Science · Physics 2016-08-22 Zeeshan Ahmad , Venkatasubramanian Viswanathan

Motivation: The clinical efficacy of antibody therapeutics critically depends on high-affinity target engagement, yet laboratory affinity-maturation campaigns are slow and costly. In computational settings, most protein language models…

Computational Engineering, Finance, and Science · Computer Science 2025-12-22 Xinyan Zhao , Yi-Ching Tang , Rivaaj Monsia , Victor J. Cantu , Ashwin Kumar Ramesh , Xiaozhong Liu , Zhiqiang An , Xiaoqian Jiang , Yejin Kim

Estimating the free energy in molecular simulation requires, implicitly or explicitly, counting how many times the system is observed in a finite region. If the simulation is biased by an external potential, the weight of the configurations…

Chemical Physics · Physics 2021-12-22 Matteo Carli , Alessandro Laio

High-throughput genetic and epigenetic data are often screened for associations with an observed phenotype. For example, one may wish to test hundreds of thousands of genetic variants, or DNA methylation sites, for an association with…

Methodology · Statistics 2017-10-20 Eric F. Lock , David B. Dunson

Understanding the principles of protein folding is a cornerstone of computational biology, with implications for drug design, bioengineering, and the understanding of fundamental biological processes. Lattice protein folding models offer a…

Disordered Systems and Neural Networks · Physics 2025-08-08 Shoummo Ahsan Khandoker , Estelle M. Inack , Mohamed Hibat-Allah

We introduce the Free Energy Manifold (FEM), a score-trained conditional energy model specialized for inference in hybrid Bayesian networks with discrete and continuous variables. FEM represents each conditional factor as an energy…

Machine Learning · Computer Science 2026-05-12 Cheol Young Park , Shou Matsumoto

We report the results of our participation in the SAMPL8 GDCC Blind Challenge for host-guest binding affinity predictions. Absolute binding affinity prediction is of central importance to the biophysics of molecular association and…

Chemical Physics · Physics 2022-02-09 Solmaz Azimi , Joe Z. Wu , Sheenam Khuttan , Tom Kurtzman , Nanjie Deng , Emilio Gallicchio

In order to establish the thermodynamic stability of a system, knowledge of its Gibbs free energy is essential. Most often, the Gibbs free energy is predicted within the CALPHAD framework using models employing thermodynamic properties,…

The alignment of the frontier orbital energies of an adsorbed molecule with the substrate Fermi level at metal-organic interfaces is a fundamental observable of significant practical importance in nanoscience and beyond. Typical density…

Mesoscale and Nanoscale Physics · Physics 2017-03-07 Zhenfei Liu , David A. Egger , Sivan Refaely-Abramson , Leeor Kronik , Jeffrey B. Neaton

Quantum chemical calculations (QCC) are computational techniques to analyze the characteristics of molecules. The variational quantum eigensolver (VQE) designed for noisy intermediate-scale quantum (NISQ) computers can be used to calculate…

Chemical Physics · Physics 2024-01-17 Satoshi Imamura , Akihiko Kasagi , Eiji Yoshida

The ability of quantum computers to overcome the exponential memory scaling of many-body problems is expected to transform quantum chemistry. Quantum algorithms require accurate representations of electronic states on a quantum device, but…

Chemical Physics · Physics 2024-04-26 Hugh G. A. Burton
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