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Structure-Based Drug Design (SBDD) is crucial for identifying bioactive molecules. Recent deep generative models are faced with challenges in geometric structure modeling. A major bottleneck lies in the twisted probability path of…

Biomolecules · Quantitative Biology 2025-06-06 Keyue Qiu , Yuxuan Song , Zhehuan Fan , Peidong Liu , Zhe Zhang , Mingyue Zheng , Hao Zhou , Wei-Ying Ma

Drug development is a critical but notoriously resource- and time-consuming process. In this manuscript, we develop a novel generative artificial intelligence (genAI) method DiffSMol to facilitate drug development. DiffSmol generates 3D…

Machine Learning · Computer Science 2025-02-11 Ziqi Chen , Bo Peng , Tianhua Zhai , Daniel Adu-Ampratwum , Xia Ning

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 2026-01-22 Kangyu Zheng , Kai Zhang , Jiale Tan , Xuehan Chen , Yingzhou Lu , Zaixi Zhang , Lichao Sun , Marinka Zitnik , Tianfan Fu , Zhiding Liang

Computational drug discovery strategies can be broadly placed in two categories: ligand-based methods which identify novel molecules by similarity with known ligands, and structure-based methods which predict molecules with high-affinity to…

Quantitative Methods · Quantitative Biology 2019-05-30 Vincent Mallet , Carlos G. Oliver , Nicolas Moitessier , Jerome Waldispuhl

Structure-based drug design involves finding ligand molecules that exhibit structural and chemical complementarity to protein pockets. Deep generative methods have shown promise in proposing novel molecules from scratch (de-novo design),…

Quantitative Methods · Quantitative Biology 2021-11-09 Pavol Drotár , Arian Rokkum Jamasb , Ben Day , Cătălina Cangea , Pietro Liò

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

Structure-based drug design (SBDD), which maps target proteins to candidate molecular ligands, is a fundamental task in drug discovery. Effectively aligning protein structural representations with molecular representations, and ensuring…

Artificial Intelligence · Computer Science 2025-11-03 Wei Zhang , Zekun Guo , Yingce Xia , Peiran Jin , Shufang Xie , Tao Qin , Xiang-Yang Li

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 drug discovery (SBDD) is a systematic scientific process that develops new drugs by leveraging the detailed physical structure of the target protein. Recent advancements in pre-trained models for biomolecules have…

Machine Learning · Computer Science 2025-03-07 Yiheng Zhu , Mingyang Li , Junlong Liu , Kun Fu , Jiansheng Wu , Qiuyi Li , Mingze Yin , Jieping Ye , Jian Wu , Zheng Wang

Several generative models with elaborate training and sampling procedures have been proposed to accelerate structure-based drug design (SBDD); however, their empirical performance turns out to be suboptimal. We seek to better understand…

Machine Learning · Computer Science 2025-03-04 Rafał Karczewski , Samuel Kaski , Markus Heinonen , Vikas Garg

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

3D generative models have shown significant promise in structure-based drug design (SBDD), particularly in discovering ligands tailored to specific target binding sites. Existing algorithms often focus primarily on ligand-target binding,…

Structure-Based drug design (SBDD) has emerged as a popular approach in drug discovery, leveraging three-dimensional protein structures to generate drug ligands. However, existing generative models encounter several key challenges: (1)…

Machine Learning · Computer Science 2025-11-27 Qingsong Zhong , Haomin Yu , Yan Lin , Wangmeng Shen , Long Zeng , Jilin Hu

The rise of cost involved with drug discovery and current speed of which they are discover, underscore the need for more efficient structure-based drug design (SBDD) methods. We employ Generative Flow Networks (GFlowNets), to effectively…

Machine Learning · Computer Science 2024-06-18 Grayson Lee , Tony Shen , Martin Ester

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

Machine learning approaches to Structure-Based Drug Design (SBDD) have proven quite fertile over the last few years. In particular, diffusion-based approaches to SBDD have shown great promise. We present a technique which expands on this…

Machine Learning · Computer Science 2024-07-01 Matan Halfon , Eyal Rozenberg , Ehud Rivlin , Daniel Freedman

Shape-based virtual screening is widely employed in ligand-based drug design to search chemical libraries for molecules with similar 3D shapes yet novel 2D chemical structures compared to known ligands. 3D deep generative models have the…

Chemical Physics · Physics 2022-10-12 Keir Adams , Connor W. Coley

Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…

Biomolecules · Quantitative Biology 2024-07-16 Haitao Lin , Yufei Huang , Odin Zhang , Siqi Ma , Meng Liu , Xuanjing Li , Lirong Wu , Jishui Wang , Tingjun Hou , Stan Z. Li

Structure-based drug design (SBDD) aims to generate potential drugs that can bind to a target protein and is greatly expedited by the aid of AI techniques in generative models. However, a lack of systematic understanding persists due to the…

Machine Learning · Computer Science 2024-10-11 Haitao Lin , Guojiang Zhao , Odin Zhang , Yufei Huang , Lirong Wu , Zicheng Liu , Siyuan Li , Cheng Tan , Zhifeng Gao , Stan Z. Li

Navigating the vast chemical space of druggable compounds is a formidable challenge in drug discovery, where generative models are increasingly employed to identify viable candidates. Conditional 3D structure-based drug design (3D-SBDD)…

Machine Learning · Computer Science 2025-02-04 Kiwoong Yoo , Owen Oertell , Junhyun Lee , Sanghoon Lee , Jaewoo Kang