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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

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

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 a ligand's bound pose to a target protein is a key component of early-stage computational drug discovery. Recent developments in machine learning methods have focused on improving pose quality at the cost of model runtime. For…

Biomolecules · Quantitative Biology 2024-10-23 Wojtek Treyde , Seohyun Chris Kim , Nazim Bouatta , Mohammed AlQuraishi

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 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

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

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

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

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

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…

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

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…

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

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

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

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

Molecular docking that predicts the bound structures of small molecules (ligands) to their protein targets, plays a vital role in drug discovery. However, existing docking methods often face limitations: they either overlook crucial…

Quantitative Methods · Quantitative Biology 2025-02-24 Zizhuo Zhang , Lijun Wu , Kaiyuan Gao , Jiangchao Yao , Tao Qin , Bo Han

The affinity and specificity of protein-molecule binding directly impact functional outcomes, uncovering the mechanisms underlying biological regulation and signal transduction. Most deep-learning-based prediction approaches focus on…

Machine Learning · Computer Science 2025-06-03 Haitao Lin , Odin Zhang , Jia Xu , Yunfan Liu , Zheng Cheng , Lirong Wu , Yufei Huang , Zhifeng Gao , Stan Z. Li
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