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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

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

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 field of machine learning for drug discovery is witnessing an explosion of novel methods. These methods are often benchmarked on simple physicochemical properties such as solubility or general druglikeness, which can be readily…

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

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…

Accurate identification of druggable pockets and their features is essential for structure-based drug design and effective downstream docking. Here, we present RAPID-Net, a deep learning-based algorithm designed for the accurate prediction…

Biomolecules · Quantitative Biology 2025-07-24 Yaroslav Balytskyi , Inna Hubenko , Alina Balytska , Christopher V. Kelly

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

Selecting an effective docking algorithm is highly context-dependent, and no single method performs reliably across structural, chemical, or protocol regimes. We introduce MolAS, a lightweight algorithm selection system that predicts…

Quantitative Methods · Quantitative Biology 2025-12-03 Jiabao Brad Wang , Siyuan Cao , Hongxuan Wu , Yiliang Yuan , Mustafa Misir

In recent years, machine learning (ML) methods have emerged as promising alternatives for molecular docking, offering the potential for high accuracy without incurring prohibitive computational costs. However, recent studies have indicated…

Biomolecules · Quantitative Biology 2024-05-21 Eric Alcaide , Zhifeng Gao , Guolin Ke , Yaqi Li , Linfeng Zhang , Hang Zheng , Gengmo Zhou

Most widely used ligand docking methods assume a rigid protein structure. This leads to problems when the structure of the target protein deforms upon ligand binding. In particular, the ligand's true binding pose is often scored very…

Biomolecules · Quantitative Biology 2023-03-22 Patricia Suriana , Joseph M. Paggi , Ron O. Dror

Molecular docking is a central method in the computer-based screening of compound libraries as a part of the rational approach to drug design. Although the method has proved its competence in predicting binding modes correctly, its inherent…

Biomolecules · Quantitative Biology 2014-04-01 Eva Kiszka

The process of screening molecules for desirable properties is a key step in several applications, ranging from drug discovery to material design. During the process of drug discovery specifically, protein-ligand docking, or chemical…

Machine Learning · Computer Science 2022-11-08 Ryien Hosseini , Filippo Simini , Austin Clyde , Arvind Ramanathan

Protein-ligand scoring is a central component of structure-based drug design, underpinning molecular docking, virtual screening, and pose optimization. Conventional physics-based energy functions are often computationally expensive,…

Biomolecules · Quantitative Biology 2026-02-24 Zhangfan Yang , Baoyun Chen , Dong Xu , Jia Wang , Ruibin Bai , Junkai Ji , Zexuan Zhu

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

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

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

Accurate prediction of protein-ligand binding poses is crucial for structure-based drug design, yet existing methods struggle to balance speed, accuracy, and physical plausibility. We introduce Matcha, a novel molecular docking pipeline…

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

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