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In silico prediction of the ligand binding pose to a given protein target is a crucial but challenging task in drug discovery. This work focuses on blind flexible selfdocking, where we aim to predict the positions, orientations and…

Biomolecules · Quantitative Biology 2023-06-02 Yangtian Zhang , Huiyu Cai , Chence Shi , Bozitao Zhong , Jian Tang

Predicting accurate protein-ligand binding affinity is important in drug discovery but remains a challenge even with computationally expensive biophysics-based energy scoring methods and state-of-the-art deep learning approaches. Despite…

There is great interest to develop artificial intelligence-based protein-ligand affinity models due to their immense applications in drug discovery. In this paper, PointNet and PointTransformer, two pointwise multi-layer perceptrons have…

Biomolecules · Quantitative Biology 2021-07-12 Yeji Wang , Shuo Wu , Yanwen Duan , Yong Huang

Protein-ligand binding is the process by which a small molecule (drug or inhibitor) attaches to a target protein. Binding affinity, which characterizes the strength of biomolecular interactions, is essential for tackling diverse challenges…

We present TerraBind, a foundation model for protein-ligand structure and binding affinity prediction that achieves 26-fold faster inference than state-of-the-art methods while improving affinity prediction accuracy by $\sim$20\%. Current…

Empirical scoring functions based on either molecular force fields or cheminformatics descriptors are widely used, in conjunction with molecular docking, during the early stages of drug discovery to predict potency and binding affinity of a…

Machine Learning · Computer Science 2017-03-31 Joseph Gomes , Bharath Ramsundar , Evan N. Feinberg , Vijay S. Pande

The accurate screening of candidate drug ligands against target proteins through computational approaches is of prime interest to drug development efforts. Such virtual screening depends in part on methods to predict the binding affinity…

Machine Learning · Computer Science 2024-10-22 Ho-Joon Lee , Prashant S. Emani , Mark B. Gerstein

Predicting how a drug-like molecule binds to a specific protein target is a core problem in drug discovery. An extremely fast computational binding method would enable key applications such as fast virtual screening or drug engineering.…

Biomolecules · Quantitative Biology 2022-06-07 Hannes Stärk , Octavian-Eugen Ganea , Lagnajit Pattanaik , Regina Barzilay , Tommi Jaakkola

Accurate prediction of protein-ligand binding affinities is crucial for drug development. Recent advances in machine learning show promising results on this task. However, these methods typically rely heavily on labeled data, which can be…

Machine Learning · Computer Science 2024-06-13 Meng Liu , Saee Gopal Paliwal

Structure based ligand discovery is one of the most successful approaches for augmenting the drug discovery process. Currently, there is a notable shift towards machine learning (ML) methodologies to aid such procedures. Deep learning has…

Machine Learning · Statistics 2018-06-12 Marta M. Stepniewska-Dziubinska , Piotr Zielenkiewicz , Pawel Siedlecki

Protein-ligand modeling underpins computational drug discovery and molecular design. Existing protein-ligand benchmarks typically evaluate whether a protein and ligand interact and how strongly they bind, through tasks such as binary…

Machine Learning · Computer Science 2026-05-26 Zhaohan Meng , Zhen Bai , Ke Yuan , Iadh Ounis , Zaiqiao Meng , Hao Xu , Joseph Loscalzo

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

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this…

Machine Learning · Computer Science 2024-01-10 Qizhi Pei , Kaiyuan Gao , Lijun Wu , Jinhua Zhu , Yingce Xia , Shufang Xie , Tao Qin , Kun He , Tie-Yan Liu , Rui Yan

Machine learning models for 3D molecular property prediction typically rely on atom-based representations, which may overlook subtle physical information. Electron density maps -- the direct output of X-ray crystallography and cryo-electron…

Machine Learning · Computer Science 2025-12-01 Patricia Suriana , Joshua A. Rackers , Ewa M. Nowara , Pedro O. Pinheiro , John M. Nicoloudis , Vishnu Sresht

Motivation: Drug discovery demands rapid quantification of compound-protein interaction (CPI). However, there is a lack of methods that can predict compound-protein affinity from sequences alone with high applicability, accuracy, and…

Biomolecules · Quantitative Biology 2020-12-17 Mostafa Karimi , Di Wu , Zhangyang Wang , Yang Shen

The cornerstone of computational drug design is the calculation of binding affinity between two biological counterparts, especially a chemical compound, i.e., a ligand, and a protein. Predicting the strength of protein-ligand binding with…

Biomolecules · Quantitative Biology 2019-12-04 Yanjun Li , Mohammad A. Rezaei , Chenglong Li , Xiaolin Li , Dapeng Wu

Protein-protein interactions (PPIs) play a crucial role in numerous biological processes. Developing methods that predict binding affinity changes under substitution mutations is fundamental for modelling and re-engineering biological…

Binding energy is a fundamental thermodynamic property that governs molecular interactions, playing a crucial role in fields such as healthcare and the natural sciences. It is particularly relevant in drug development, vaccine design, and…

Quantum Physics · Physics 2025-08-06 Erico Souza Teixeira , Lucas Barros Fernandes , Yara Rodrigues Inácio

The pretrain-finetune paradigm has achieved great success in NLP and 2D image fields because of the high-quality representation ability and transferability of their pretrained models. However, pretraining such a strong model is difficult in…

Computer Vision and Pattern Recognition · Computer Science 2023-12-12 Xiaoshui Huang , Zhou Huang , Sheng Li , Wentao Qu , Tong He , Yuenan Hou , Yifan Zuo , Wanli Ouyang

Predicting the docking between proteins and ligands is a crucial and challenging task for drug discovery. However, traditional docking methods mainly rely on scoring functions, and deep learning-based docking approaches usually neglect the…

Biomolecules · Quantitative Biology 2026-01-06 Yiqiang Yi , Xu Wan , Yatao Bian , Le Ou-Yang , Peilin Zhao
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