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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

Accurate prediction of protein-ligand binding affinity is critical for drug discovery. While recent deep learning approaches have demonstrated promising results, they often rely solely on structural features of proteins and ligands,…

Machine Learning · Computer Science 2026-01-23 Han Liu , Keyan Ding , Peilin Chen , Yinwei Wei , Liqiang Nie , Dapeng Wu , Shiqi Wang

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…

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…

Prediction of protein-ligand interactions (PLI) plays a crucial role in drug discovery as it guides the identification and optimization of molecules that effectively bind to target proteins. Despite remarkable advances in deep…

Biomolecules · Quantitative Biology 2023-07-18 Seokhyun Moon , Sang-Yeon Hwang , Jaechang Lim , Woo Youn Kim

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

The binding between proteins and ligands plays a crucial role in the realm of drug discovery. Previous deep learning approaches have shown promising results over traditional computationally intensive methods, but resulting in poor…

Biomolecules · Quantitative Biology 2023-11-29 Shikun Feng , Minghao Li , Yinjun Jia , Weiying Ma , Yanyan Lan

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…

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

Accurate prediction of protein-ligand binding affinity is crucial for rapid and efficient drug development. Recently, the importance of predicting binding affinity has led to increased attention on research that models the three-dimensional…

Machine Learning · Computer Science 2024-07-17 Seungyeon Choi , Sangmin Seo , Sanghyun Park

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

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

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

Protein-ligand binding prediction is central to virtual screening and affinity ranking, two fundamental tasks in drug discovery. While recent retrieval-based methods embed ligands and protein pockets into Euclidean space for…

Machine Learning · Computer Science 2025-11-25 Jianhui Wang , Wenyu Zhu , Bowen Gao , Xin Hong , Ya-Qin Zhang , Wei-Ying Ma , Yanyan Lan

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

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

Determination of binding affinity of proteins in the formation of protein complexes requires sophisticated, expensive and time-consuming experimentation which can be replaced with computational methods. Most computational prediction…

Quantitative Methods · Quantitative Biology 2020-12-14 Wajid Arshad Abbasi , Fahad Ul Hassan , Adiba Yaseen , Fayyaz Ul Amir Afsar Minhas

Accurate prediction of protein-ligand binding affinity remains a central challenge in structure-based drug discovery. The effectiveness of machine learning models critically depends on the quality of molecular descriptors, for which…

Biomolecules · Quantitative Biology 2026-03-24 Jian Liu , Hongsong Feng

Prediction of protein-ligand binding affinity is a major goal in drug discovery. Generally, free energy gap is calculated between two states (e.g., ligand binding and unbinding). The energy gap implicitly includes the effects of changes in…

Biomolecules · Quantitative Biology 2022-05-20 Ikki Yasuda , Katsuhiro Endo , Eiji Yamamoto , Yoshinori Hirano , Kenji Yasuoka

Drug discovery often relies on the successful prediction of protein-ligand binding affinity. Recent advances have shown great promise in applying graph neural networks (GNNs) for better affinity prediction by learning the representations of…

Quantitative Methods · Quantitative Biology 2021-07-24 Shuangli Li , Jingbo Zhou , Tong Xu , Liang Huang , Fan Wang , Haoyi Xiong , Weili Huang , Dejing Dou , Hui Xiong
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