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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

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 advances in generative models, particularly diffusion and auto-regressive models, have revolutionized fields like computer vision and natural language processing. However, their application to structure-based drug design (SBDD)…

Machine Learning · Computer Science 2025-07-29 Yi He , Ailun Wang , Zhi Wang , Yu Liu , Xingyuan Xu , Wen 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

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

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) 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

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) 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

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

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

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

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

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

To generate drug molecules of desired properties with computational methods is the holy grail in pharmaceutical research. Here we describe an AI strategy, retro drug design, or RDD, to generate novel small molecule drugs from scratch to…

Biomolecules · Quantitative Biology 2021-05-12 Yuhong Wang , Sam Michael , Ruili Huang , Jinghua Zhao , Katlin Recabo , Danielle Bougie , Qiang Shu , Paul Shinn , Hongmao Sun

Structure-based molecular ML (SBML) models can be highly sensitive to input geometries and give predictions with large variance. We present an approach to mitigate the challenge of selecting conformations for such models by generating…

Machine Learning · Computer Science 2023-11-08 Michael Maser , Natasa Tagasovska , Jae Hyeon Lee , Andrew Watkins

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 molecule optimization (SBMO) aims to optimize molecules with both continuous coordinates and discrete types against protein targets. A promising direction is to exert gradient guidance on generative models given its…

Biomolecules · Quantitative Biology 2025-06-06 Keyue Qiu , Yuxuan Song , Jie Yu , Hongbo Ma , Ziyao Cao , Zhilong Zhang , Yushuai Wu , Mingyue Zheng , Hao Zhou , Wei-Ying Ma

We present VoxBind, a new score-based generative model for 3D molecules conditioned on protein structures. Our approach represents molecules as 3D atomic density grids and leverages a 3D voxel-denoising network for learning and generation.…

Machine Learning · Computer Science 2024-07-03 Pedro O. Pinheiro , Arian Jamasb , Omar Mahmood , Vishnu Sresht , Saeed Saremi

Predicting the binding structure of a small molecule ligand to a protein -- a task known as molecular docking -- is critical to drug design. Recent deep learning methods that treat docking as a regression problem have decreased runtime…

Biomolecules · Quantitative Biology 2023-02-14 Gabriele Corso , Hannes Stärk , Bowen Jing , Regina Barzilay , Tommi Jaakkola