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Structure-based drug design (SBDD) aims to design small-molecule ligands that bind with high affinity and specificity to pre-determined protein targets. Generative SBDD methods leverage structural data of drugs in complex with their protein…

Structure-Based Drug Design (SBDD) has revolutionized drug discovery by enabling the rational design of molecules for specific protein targets. Despite significant advancements in improving docking scores, advanced 3D-SBDD generative models…

Biomolecules · Quantitative Biology 2025-03-04 Bowen Gao , Yanwen Huang , Yiqiao Liu , Wenxuan Xie , Wei-Ying Ma , Ya-Qin Zhang , Yanyan Lan

Structure-based drug design (SBDD) leverages the three-dimensional geometry of proteins to identify potential drug candidates. Traditional approaches, rooted in physicochemical modeling and domain expertise, are often resource-intensive.…

Quantitative Methods · Quantitative Biology 2024-11-19 Zaixi Zhang , Jiaxian Yan , Yining Huang , Qi Liu , Enhong Chen , Mengdi Wang , Marinka Zitnik

Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to…

Biomolecules · Quantitative Biology 2024-03-01 Zhilin Huang , Ling Yang , Zaixi Zhang , Xiangxin Zhou , Yu Bao , Xiawu Zheng , Yuwei Yang , Yu Wang , Wenming Yang

Structure-based drug design (SBDD) is crucial for developing specific and effective therapeutics against protein targets but remains challenging due to complex protein-ligand interactions and vast chemical space. Although language models…

Biomolecules · Quantitative Biology 2024-08-20 Cong Fu , Xiner Li , Blake Olson , Heng Ji , Shuiwang Ji

Structure-based drug design (SBDD) is a critical task in drug discovery, requiring the generation of molecular information across two distinct modalities: discrete molecular graphs and continuous 3D coordinates. However, existing SBDD…

Computational Engineering, Finance, and Science · Computer Science 2025-03-28 Xiuyuan Hu , Guoqing Liu , Can Chen , Yang Zhao , Hao Zhang , Xue Liu

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 aims at generating high affinity ligands with prior knowledge of 3D target structures. Existing methods either use conditional generative model to learn the distribution of 3D ligands given target binding sites,…

Biomolecules · Quantitative Biology 2024-03-18 Yuwei Yang , Siqi Ouyang , Xueyu Hu , Mingyue Zheng , Hao Zhou , Lei Li

Deep generative models have achieved tremendous success in structure-based drug design in recent years, especially for generating 3D ligand molecules that bind to specific protein pocket. Notably, diffusion models have transformed ligand…

Machine Learning · Computer Science 2024-12-03 Daiheng Zhang , Chengyue Gong , Qiang Liu

Recent remarkable advancements in geometric deep generative models, coupled with accumulated structural data, enable structure-based drug design (SBDD) using only target protein information. However, existing models often struggle to…

Biomolecules · Quantitative Biology 2026-03-09 Joongwon Lee , Wonho Zhung , Jisu Seo , Woo Youn Kim

Structure-based drug design (SBDD) aims to discover drug candidates by finding molecules (ligands) that bind tightly to a disease-related protein (targets), which is the primary approach to computer-aided drug discovery. Recently, applying…

Quantitative Methods · Quantitative Biology 2022-12-01 Tianfan Fu , Wenhao Gao , Connor W. Coley , Jimeng Sun

We study a fundamental problem in structure-based drug design -- generating molecules that bind to specific protein binding sites. While we have witnessed the great success of deep generative models in drug design, the existing methods are…

Biomolecules · Quantitative Biology 2022-11-15 Shitong Luo , Jiaqi Guan , Jianzhu Ma , Jian Peng

Structure-based drug design (SBDD) aims to generate ligands that bind strongly and specifically to target protein pockets. Recent diffusion models have advanced SBDD by capturing the distributions of atomic positions and types, yet they…

Machine Learning · Computer Science 2026-02-11 Yue Jian , Curtis Wu , Danny Reidenbach , Aditi S. Krishnapriyan

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) 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

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

Deep generative models for structure-based drug design (SBDD), where molecule generation is conditioned on a 3D protein pocket, have received considerable interest in recent years. These methods offer the promise of higher-quality molecule…

Biomolecules · Quantitative Biology 2023-08-16 Charles Harris , Kieran Didi , Arian R. Jamasb , Chaitanya K. Joshi , Simon V. Mathis , Pietro Lio , Tom Blundell

Structure-Based Drug Design (SBDD) is a powerful strategy in computational drug discovery, utilizing three-dimensional protein structures to guide the design of molecules with improved binding affinity. However, capturing complex…

Machine Learning · Computer Science 2025-11-18 Long Xu , Yongcai Chen , Fengshuo Liu , Yuzhong Peng

Structure-based drug design (SBDD) faces a fundamental scaling fidelity dilemma: rich pocket-aware conditioning captures interaction geometry but can be costly, often scales quadratically ($O(L^2)$) or worse with protein length ($L$), while…

Machine Learning · Computer Science 2026-02-02 Samyak Sanghvi , Nishant Ranjan , Tarak Karmakar

Finding drug-like compounds with high bioactivity is essential for drug discovery, but the task is complicated by the high cost of chemical synthesis and validation. With their outstanding performance in de novo drug design, deep generative…

Quantitative Methods · Quantitative Biology 2023-01-03 Yibo Li , Jianfeng Pei , Luhua Lai
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