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Protein-ligand binding prediction is a fundamental problem in AI-driven drug discovery. Prior work focused on supervised learning methods using a large set of binding affinity data for small molecules, but it is hard to apply the same…

Biomolecules · Quantitative Biology 2023-12-14 Wengong Jin , Siranush Sarkizova , Xun Chen , Nir Hacohen , Caroline Uhler

The field of protein-ligand pose prediction has seen significant advances in recent years, with machine learning-based methods now being commonly used in lieu of classical docking methods or even to predict all-atom protein-ligand complex…

Biomolecules · Quantitative Biology 2024-10-01 David Errington , Constantin Schneider , Cédric Bouysset , Frédéric A. Dreyer

The primary objective of most lead optimization campaigns is to enhance the binding affinity of ligands. For large molecules such as antibodies, identifying mutations that enhance antibody affinity is particularly challenging due to the…

Machine Learning · Computer Science 2024-06-12 Alexandra Gessner , Sebastian W. Ober , Owen Vickery , Dino Oglić , Talip Uçar

Simulating drug binding and unbinding is a challenge, as the rugged energy landscapes that separate bound and unbound states require extensive sampling that consumes significant computational resources. Here, we describe the use of…

The prediction of protein-ligand binding affinity is of great significance for discovering lead compounds in drug research. Facing this challenging task, most existing prediction methods rely on the topological and/or spatial structure of…

Biomolecules · Quantitative Biology 2022-09-28 Yang Zhang , Gengmo Zhou , Zhewei Wei , Hongteng Xu

Computational docking is the core process of computer-aided drug design; it aims at predicting the best orientation and conformation of a small drug molecule when bound to a target large protein receptor. The docking quality is typically…

Biomolecules · Quantitative Biology 2016-08-25 Mohamed Khamis , Walid Gomaa , Basem Galal

Molecular dynamics simulations have emerged as a fundamental instrument for studying biomolecules. At the same time, it is desirable to perform simulations of a collection of particles under various conditions in which the molecules can…

Machine Learning · Computer Science 2023-10-11 Jingbang Chen , Yian Wang , Xingwei Qu , Shuangjia Zheng , Yaodong Yang , Hao Dong , Jie Fu

Protein-ligand structure prediction is an essential task in drug discovery, predicting the binding interactions between small molecules (ligands) and target proteins (receptors). Recent advances have incorporated deep learning techniques to…

Machine learned interaction potentials (MLIPs) have become a critical component of large-scale, high-quality simulations for a range of chemical and biochemical systems. Yet, despite their in-distribution accuracy, molecular dynamics…

Chemical Physics · Physics 2026-04-09 Eric C. -Y. Yuan , Teresa Head-Gordon

Accurate prediction and optimization of protein-protein binding affinity is crucial for therapeutic antibody development. Although machine learning-based prediction methods $\Delta\Delta G$ are suitable for large-scale mutant screening,…

Biomolecules · Quantitative Biology 2024-09-19 Kairi Furui , Masahito Ohue

The field of drug discovery hinges on the accurate prediction of binding affinity between prospective drug molecules and target proteins, especially when such proteins directly influence disease progression. However, estimating binding…

The protein-ligand binding affinity (PLA) prediction goal is to predict whether or not the ligand could bind to a protein sequence. Recently, in PLA prediction, deep learning has received much attention. Two steps are involved in deep…

Quantitative Methods · Quantitative Biology 2024-05-21 Karim Abbasi , Parvin Razzaghi , Amin Ghareyazi , Hamid R. Rabiee

Development of scoring functions (SFs) used to predict protein-ligand binding energies requires high-quality 3D structures and binding assay data for training and testing their parameters. In this work, we show that one of the widely-used…

Biological Physics · Physics 2025-03-10 Yingze Wang , Kunyang Sun , Jie Li , Xingyi Guan , Oufan Zhang , Dorian Bagni , Teresa Head-Gordon

The characterization of drug-protein interactions is crucial in the high-throughput screening for drug discovery. The deep learning-based approaches have attracted attention because they can predict drug-protein interactions without…

Machine Learning · Computer Science 2020-12-22 QHwan Kim , Joon-Hyuk Ko , Sunghoon Kim , Nojun Park , Wonho Jhe

In structure-based drug design, accurately estimating the binding affinity between a candidate ligand and its protein receptor is a central challenge. Recent advances in artificial intelligence, particularly deep learning, have demonstrated…

Biomolecules · Quantitative Biology 2025-09-18 Md Masud Rana , Farjana Tasnim Mukta , Duc D. Nguyen

Predicting protein-ligand binding affinity remains intractable for multi-domain proteins, where inter-domain dynamics govern molecular recognition. Existing geometric deep learning methods typically treat proteins as monolithic static…

Machine Learning · Computer Science 2026-05-20 Shuo Zhang , Rongqi Hong , Huifeng Zhang , Jian K. Liu

Ligands entering a protein binding pocket essentially compete with water molecules for binding to the protein. Hence, the location and thermodynamic properties of water molecules in protein structures have gained increased attention in the…

Biomolecules · Quantitative Biology 2019-08-28 David Schaller , Szymon Pach , Gerhard Wolber

Protein-ligand binding complexes are ubiquitous and essential to life. Protein-ligand binding affinity prediction (PLA) quantifies the binding strength between ligands and proteins, providing crucial insights for discovering and designing…

Computational Engineering, Finance, and Science · Computer Science 2025-04-24 Krinos Li , Xianglu Xiao , Zijun Zhong , Guang Yang

Accurately predicting the binding conformation of small-molecule ligands to protein targets is a critical step in rational drug design. Although recent deep learning-based docking surpasses traditional methods in speed and accuracy, many…

Computer Vision and Pattern Recognition · Computer Science 2025-08-14 Liyan Jia , Chuan-Xian Ren , Hong Yan

Numerous cellular functions rely on protein$\unicode{x2013}$protein interactions. Efforts to comprehensively characterize them remain challenged however by the diversity of molecular recognition mechanisms employed within the proteome. Deep…

Biomolecules · Quantitative Biology 2023-12-08 Julia R. Rogers , Gergő Nikolényi , Mohammed AlQuraishi