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Accurate identification of protein nucleic-acid-binding residues poses a significant challenge with important implications for various biological processes and drug design. Many typical computational methods for protein analysis rely on a…

Biomolecules · Quantitative Biology 2023-12-21 Linglin Jing , Sheng Xu , Yifan Wang , Yuzhe Zhou , Tao Shen , Zhigang Ji , Hui Fang , Zhen Li , Siqi Sun

Modern AI technologies for drug discovery are distributed across heterogeneous platforms-including web applications, desktop environments, and code libraries-leading to fragmented workflows, inconsistent interfaces, and high integration…

The dynamic nature of proteins, influenced by ligand interactions, is essential for comprehending protein function and progressing drug discovery. Traditional structure-based drug design (SBDD) approaches typically target binding sites with…

Biomolecules · Quantitative Biology 2025-03-07 Xiangxin Zhou , Yi Xiao , Haowei Lin , Xinheng He , Jiaqi Guan , Yang Wang , Qiang Liu , Feng Zhou , Liang Wang , Jianzhu Ma

Structure-based drug design (SBDD) focuses on designing small-molecule ligands that bind to specific protein pockets. Computational methods are integral in modern SBDD workflows and often make use of virtual screening methods via docking or…

Machine Learning · Computer Science 2025-12-05 Ian Dunn , Liv Toft , Tyler Katz , Juhi Gupta , Riya Shah , Ramith Hettiarachchi , David R. Koes

Understanding the kinetics of drug-protein interactions is paramount for drug design, yet the field lacks large-scale, dynamic data to move beyond static structural analysis. Here, we present DD-03B, a massively scalable database providing…

Computational Physics · Physics 2026-04-09 Maodong Li , Dechin Chen , Zhijun Pan , Zhe Wang , Yi Isaac Yang

Self-supervised semantic segmentation methods often suffer from structural errors, including merging distinct objects or fragmenting coherent regions, because they rely primarily on low-level appearance cues such as color and texture. These…

Computer Vision and Pattern Recognition · Computer Science 2026-03-17 Haotang Li , Zhenyu Qi , Hao Qin , Huanrui Yang , Kebin Peng , Qing Guo , Sen He

Structure-based drug design (SBDD), which aims to generate molecules that can bind tightly to the target protein, is an essential problem in drug discovery, and previous approaches have achieved initial success. However, most existing…

Machine Learning · Computer Science 2024-04-04 Xinze Li , Penglei Wang , Tianfan Fu , Wenhao Gao , Chengtao Li , Leilei Shi , Junhong Liu

Structure-based drug design (SBDD) stands at the forefront of drug discovery, emphasizing the creation of molecules that target specific binding pockets. Recent advances in this area have witnessed the adoption of deep generative models and…

Quantitative Methods · Quantitative Biology 2023-11-22 Minsi Ren , Bowen Gao , Bo Qiang , Yanyan Lan

Accurate prediction of the binding affinity between drugs and target proteins is a core task in computer-aided drug design. Existing deep learning methods tend to ignore the information of internal sub-structural features of drug molecules…

Biomolecules · Quantitative Biology 2025-04-04 Jiannuo Li , Lan Yao

Generating molecules with high binding affinities to target proteins (a.k.a. structure-based drug design) is a fundamental and challenging task in drug discovery. Recently, deep generative models have achieved remarkable success in…

Biomolecules · Quantitative Biology 2023-05-24 Zaixi Zhang , Qi Liu

Currently, the field of structure-based drug design is dominated by three main types of algorithms: search-based algorithms, deep generative models, and reinforcement learning. While existing works have typically focused on comparing models…

Machine Learning · Computer Science 2024-06-06 Kangyu Zheng , Yingzhou Lu , Zaixi Zhang , Zhongwei Wan , Yao Ma , Marinka Zitnik , Tianfan Fu

Accurate identification of drug-target interactions (DTI) remains a central challenge in computational pharmacology, where sequence-based methods offer scalability. This work introduces a sequence-based drug-target interaction framework…

Large Language Models (LLMs) possess strong representation and reasoning capabilities, but their application to structure-based drug design (SBDD) is limited by insufficient understanding of protein structures and unpredictable molecular…

Machine Learning · Computer Science 2026-01-27 Xuanning Hu , Anchen Li , Qianli Xing , Jinglong Ji , Hao Tuo , Bo Yang

Protein (receptor)--ligand interaction prediction is a critical component in computer-aided drug design, significantly influencing molecular docking and virtual screening processes. Despite the development of numerous scoring functions in…

Biomolecules · Quantitative Biology 2024-01-22 Haoyu Lin , Shiwei Wang , Jintao Zhu , Yibo Li , Jianfeng Pei , Luhua Lai

Drug combination therapies have shown promising therapeutic efficacy in complex diseases and have demonstrated the potential to reduce drug resistance. However, the huge number of possible drug combinations makes it difficult to screen them…

Machine Learning · Computer Science 2025-01-15 XinXin Ge , Yi-Ting Lee , Shan-Ju Yeh

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 drug target interactions is critical for accelerating drug discovery and elucidating complex biological mechanisms. In this work, we frame drug target prediction as a link prediction task on heterogeneous biomedical…

Computation and Language · Computer Science 2025-03-12 Haji Gul , Abdul Ghani Naim , Ajaz Ahmad Bhat

Structure-based drug design uses three-dimensional geometric information of macromolecules, such as proteins or nucleic acids, to identify suitable ligands. Geometric deep learning, an emerging concept of neural-network-based machine…

Chemical Physics · Physics 2022-10-21 Clemens Isert , Kenneth Atz , Gisbert Schneider

Designing protein-binding proteins with high affinity is critical in biomedical research and biotechnology. Despite recent advancements targeting specific proteins, the ability to create high-affinity binders for arbitrary protein targets…

Machine Learning · Computer Science 2025-11-03 Zhenqiao Song , Tiaoxiao Li , Lei Li , Martin Renqiang Min

Recent pre-training strategies for molecular graphs have attempted to use 2D and 3D molecular views as both inputs and self-supervised signals, primarily aligning graph-level representations. However, existing studies remain limited in…

Machine Learning · Computer Science 2025-11-25 Van Thuy Hoang , O-Joun Lee