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Being able to identify regions within or around proteins, to which ligands can potentially bind, is an essential step to develop new drugs. Binding site identification methods can now profit from the availability of large amounts of 3D…

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

Understanding the structure of the protein-ligand complex is crucial to drug development. Existing virtual structure measurement and screening methods are dominated by docking and its derived methods combined with deep learning. However,…

Artificial Intelligence · Computer Science 2024-08-22 Kelei He , Tiejun Dong , Jinhui Wu , Junfeng Zhang

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

Accurate prediction of protein-ligand binding affinities is an essential challenge in structure-based drug design. Despite recent advances in data-driven methods for affinity prediction, their accuracy is still limited, partially because…

Biomolecules · Quantitative Biology 2024-09-04 Yaosen Min , Ye Wei , Peizhuo Wang , Xiaoting Wang , Han Li , Nian Wu , Stefan Bauer , Shuxin Zheng , Yu Shi , Yingheng Wang , Ji Wu , Dan Zhao , Jianyang Zeng

Accurate prediction of drug-target binding affinity can accelerate drug discovery by prioritizing promising compounds before costly wet-lab screening. While deep learning has advanced this task, most models fuse ligand and protein…

Machine Learning · Computer Science 2025-09-26 Mohammadsaleh Refahi , Bahrad A. Sokhansanj , James R. Brown , Gail Rosen

Rich data and powerful machine learning models allow us to design drugs for a specific protein target \textit{in silico}. Recently, the inclusion of 3D structures during targeted drug design shows superior performance to other target-free…

Biomolecules · Quantitative Biology 2023-03-08 Jiaqi Guan , Wesley Wei Qian , Xingang Peng , Yufeng Su , Jian Peng , Jianzhu Ma

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

Protein complex formation is a central problem in biology, being involved in most of the cell's processes, and essential for applications, e.g. drug design or protein engineering. We tackle rigid body protein-protein docking, i.e.,…

Artificial Intelligence · Computer Science 2022-03-16 Octavian-Eugen Ganea , Xinyuan Huang , Charlotte Bunne , Yatao Bian , Regina Barzilay , Tommi Jaakkola , Andreas Krause

Publicly available collections of drug-like molecules have grown to comprise 10s of billions of possibilities in recent history due to advances in chemical synthesis. Traditional methods for identifying "hit" molecules from a large…

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

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

The identification of novel drug-target (DT) interactions is a substantial part of the drug discovery process. Most of the computational methods that have been proposed to predict DT interactions have focused on binary classification, where…

Machine Learning · Statistics 2019-02-06 Hakime Öztürk , Elif Ozkirimli , Arzucan Özgür

The latest biological findings observe that the traditional motionless 'lock-and-key' theory is not generally applicable because the receptor and ligand are constantly moving. Nonetheless, remarkable changes in associated atomic sites and…

Computational Engineering, Finance, and Science · Computer Science 2023-11-01 Fang Wu , Shuting Jin , Yinghui Jiang , Xurui Jin , Bowen Tang , Zhangming Niu , Xiangrong Liu , Qiang Zhang , Xiangxiang Zeng , Stan Z. Li

Molecular conformation generation plays key roles in computational drug design. Recently developed deep learning methods, particularly diffusion models have reached competitive performance over traditional cheminformatical approaches.…

Machine Learning · Computer Science 2025-01-10 Yixuan Yang , Xingyu Fang , Zhaowen Cheng , Pengju Yan , Xiaolin Li

Molecular docking, a key technique in structure-based drug design, plays pivotal roles in protein-ligand interaction modeling, hit identification and optimization, in which accurate prediction of protein-ligand binding mode is essential.…

Biomolecules · Quantitative Biology 2023-12-20 Jintao Zhu , Zhonghui Gu , Jianfeng Pei , Luhua Lai

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

Binding affinity prediction of three-dimensional (3D) protein ligand complexes is critical for drug repositioning and virtual drug screening. Existing approaches transform a 3D protein-ligand complex to a two-dimensional (2D) graph, and…

Biomolecules · Quantitative Biology 2022-10-31 Yiqiang Yi , Xu Wan , Kangfei Zhao , Le Ou-Yang , Peilin Zhao

Cancer is the second leading cause of death, with chemotherapy as one of the primary forms of treatment. As a result, researchers are turning to drug combination therapy to decrease drug resistance and increase efficacy. Current methods of…

Quantitative Methods · Quantitative Biology 2024-11-08 Zachary Schwehr

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