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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

The study of rigid protein-protein docking plays an essential role in a variety of tasks such as drug design and protein engineering. Recently, several learning-based methods have been proposed for the task, exhibiting much faster docking…

Machine Learning · Computer Science 2024-01-18 Ziyang Yu , Wenbing Huang , Yang Liu

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

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

Prediction of protein-ligand complexes for flexible proteins remains still a challenging problem in computational structural biology and drug design. Here we present two novel deep neural network approaches with significant improvement in…

Biomolecules · Quantitative Biology 2020-08-28 Amr H. Mahmoud , Jonas F. Lill , Markus A. Lill

We present a simple, modular graph-based convolutional neural network that takes structural information from protein-ligand complexes as input to generate models for activity and binding mode prediction. Complex structures are generated by…

Biomolecules · Quantitative Biology 2020-02-26 Joseph A. Morrone , Jeffrey K. Weber , Tien Huynh , Heng Luo , Wendy D. Cornell

Predicting the binding sites of target proteins plays a fundamental role in drug discovery. Most existing deep-learning methods consider a protein as a 3D image by spatially clustering its atoms into voxels and then feed the voxelized…

Biomolecules · Quantitative Biology 2024-07-24 Yang Zhang , Zhewei Wei , Ye Yuan , Chongxuan Li , Wenbing Huang

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…

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 structures, a task known as molecular docking is crucial for drug design but remains challenging. While deep learning has shown promise, existing methods often depend on holo-protein structures…

Biomolecules · Quantitative Biology 2024-02-22 Yufei Huang , Odin Zhang , Lirong Wu , Cheng Tan , Haitao Lin , Zhangyang Gao , Siyuan Li , Stan. Z. Li

Molecular docking, a technique for predicting ligand binding poses, is crucial in structure-based drug design for understanding protein-ligand interactions. Recent advancements in docking methods, particularly those leveraging geometric…

Biomolecules · Quantitative Biology 2024-10-17 Jiaxian Yan , Zaixi Zhang , Jintao Zhu , Kai Zhang , Jianfeng Pei , Qi Liu

Predicting the binding structure of a small molecule ligand to a protein -- a task known as molecular docking -- is critical to drug design. Recent deep learning methods that treat docking as a regression problem have decreased runtime…

Biomolecules · Quantitative Biology 2023-02-14 Gabriele Corso , Hannes Stärk , Bowen Jing , Regina Barzilay , Tommi Jaakkola

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

Determining the binding pose of a ligand to a protein, known as molecular docking, is a fundamental task in drug discovery. Generative approaches promise faster, improved, and more diverse pose sampling than physics-based methods, but are…

Machine Learning · Computer Science 2026-03-26 Alvaro Prat , Leo Zhang , Charlotte M. Deane , Yee Whye Teh , Garrett M. Morris

The effects of ligand binding on protein structures and their in vivo functions carry numerous implications for modern biomedical research and biotechnology development efforts such as drug discovery. Although several deep learning (DL)…

Machine Learning · Computer Science 2026-03-24 Alex Morehead , Nabin Giri , Jian Liu , Pawan Neupane , Jianlin Cheng

Molecular docking plays a crucial role in predicting the binding mode of ligands to target proteins, and covalent interactions, which involve the formation of a covalent bond between the ligand and the target, are particularly valuable due…

Biomolecules · Quantitative Biology 2025-06-27 Yangzhe Peng , Kaiyuan Gao , Liang He , Yuheng Cong , Haiguang Liu , Kun He , Lijun Wu

De novo ligand design is a fundamental task that seeks to generate protein or molecule candidates that can effectively dock with protein receptors and achieve strong binding affinity entirely from scratch. It holds paramount significance…

Machine Learning · Computer Science 2025-10-13 Zekai Chen , Xunkai Li , Sirui Zhang , Henan Sun , Jia Li , Zhenjun Li , Bing Zhou , Rong-Hua Li , Guoren Wang

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

The generation of small molecule candidate (ligand) binding poses in its target protein pocket is important for computer-aided drug discovery. Typical rigid-body docking methods ignore the pocket flexibility of protein, while the more…

Neural and Evolutionary Computing · Computer Science 2023-08-03 Jonathan P. Mailoa , Zhaofeng Ye , Jiezhong Qiu , Chang-Yu Hsieh , Shengyu Zhang

Molecular docking is a key task in computational biology that has attracted increasing interest from the machine learning community. While existing methods have achieved success, they generally treat each protein-ligand pair in isolation.…

Biomolecules · Quantitative Biology 2025-01-28 Jiaqi Guan , Jiahan Li , Xiangxin Zhou , Xingang Peng , Sheng Wang , Yunan Luo , Jian Peng , Jianzhu Ma
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