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Accurate identification of protein binding sites is crucial for understanding biomolecular interaction mechanisms and for the rational design of drug targets. Traditional predictive methods often struggle to balance prediction accuracy with…

Machine Learning · Computer Science 2026-01-06 Weisen Yang , Hanqing Zhang , Wangren Qiu , Xuan Xiao , Weizhong Lin

Generating molecular structures with desired properties is a critical task with broad applications in drug discovery and materials design. We propose 3M-Diffusion, a novel multi-modal molecular graph generation method, to generate diverse,…

Machine Learning · Computer Science 2024-10-04 Huaisheng Zhu , Teng Xiao , Vasant G Honavar

Three-dimensional molecular structure generation is typically performed at the level of individual atoms, yet molecular graph generation techniques often consider fragments as their structural units. Building on the advances in frame-based…

Machine Learning · Computer Science 2026-01-26 Roman Poletukhin , Marcel Kollovieh , Eike Eberhard , Stephan Günnemann

Proteins in complex with small molecule ligands represent the core of structure-based drug discovery. However, three-dimensional representations are absent from most deep-learning-based generative models. We here present a graph-based…

Biomolecules · Quantitative Biology 2022-04-07 Seung-gu Kang , Jeffrey K. Weber , Joseph A. Morrone , Leili Zhang , Tien Huynh , Wendy D. Cornell

Generative models of 3D molecular structure play a rapidly growing role in the design and simulation of molecules. Diffusion models currently dominate the space of 3D molecule generation, while autoregressive models have trailed behind. In…

Machine Learning · Computer Science 2025-09-10 Austin H. Cheng , Chong Sun , Alán Aspuru-Guzik

Generative AI presents chemists with novel ideas for drug design and facilitates the exploration of vast chemical spaces. Diffusion models (DMs), an emerging tool, have recently attracted great attention in drug R\&D. This paper…

Biomolecules · Quantitative Biology 2025-07-14 Peining Zhang , Daniel Baker , Minghu Song , Jinbo Bi

In the scope of drug discovery, the molecular design aims to identify novel compounds from the chemical space where the potential drug-like molecules are estimated to be in the order of 10^60 - 10^100. Since this search task is…

Machine Learning · Computer Science 2022-10-25 Wenlu Wang , Ye Wang , Honggang Zhao , Simone Sciabola

Creating realistic 3D objects and clothed avatars from a single RGB image is an attractive yet challenging problem. Due to its ill-posed nature, recent works leverage powerful prior from 2D diffusion models pretrained on large datasets.…

Computer Vision and Pattern Recognition · Computer Science 2025-11-27 Yuxuan Xue , Xianghui Xie , Riccardo Marin , Gerard Pons-Moll

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

Embedding molecular symmetries into machine-learning models is key for efficient learning of chemico-physical scalar properties, but little evidence on how to extend the same strategy to tensorial quantities exists. Here we formulate a…

Materials Science · Physics 2022-04-27 Vu Ha Anh Nguyen , Alessandro Lunghi

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

Automating molecular design using deep reinforcement learning (RL) has the potential to greatly accelerate the search for novel materials. Despite recent progress on leveraging graph representations to design molecules, such methods are…

Machine Learning · Statistics 2021-06-08 Gregor N. C. Simm , Robert Pinsler , Gábor Csányi , José Miguel Hernández-Lobato

Molecular structure elucidation from spectra is a fundamental challenge in molecular science. Conventional approaches rely heavily on expert interpretation and lack scalability, while retrieval-based machine learning approaches remain…

Machine Learning · Computer Science 2025-11-06 Liang Wang , Yu Rong , Tingyang Xu , Zhenyi Zhong , Zhiyuan Liu , Pengju Wang , Deli Zhao , Qiang Liu , Shu Wu , Liang Wang , Yang Zhang

Denoising diffusion models have shown great potential in multiple research areas. Existing diffusion-based generative methods on de novo 3D molecule generation face two major challenges. Since majority heavy atoms in molecules allow…

Machine Learning · Computer Science 2024-04-23 Can Xu , Haosen Wang , Weigang Wang , Pengfei Zheng , Hongyang Chen

Generative models, especially diffusion models (DMs), have achieved promising results for generating feature-rich geometries and advancing foundational science problems such as molecule design. Inspired by the recent huge success of Stable…

Machine Learning · Computer Science 2023-05-03 Minkai Xu , Alexander Powers , Ron Dror , Stefano Ermon , Jure Leskovec

Goal-directed molecular generation requires satisfying heterogeneous constraints such as protein--ligand compatibility and multi-objective drug-like properties, yet existing methods often optimize these constraints in isolation, failing to…

Machine Learning · Computer Science 2026-04-14 Yanting Li , Zhuoyang Jiang , Enyan Dai , Lei Wang , Wen-Cai Ye , Li Liu

The cornerstone of computational drug design is the calculation of binding affinity between two biological counterparts, especially a chemical compound, i.e., a ligand, and a protein. Predicting the strength of protein-ligand binding with…

Biomolecules · Quantitative Biology 2019-12-04 Yanjun Li , Mohammad A. Rezaei , Chenglong Li , Xiaolin Li , Dapeng Wu

Binding affinity prediction of three-dimensional (3D) protein ligand complexes is critical for drug repositioning and virtual drug screening. Existing approaches transform a 3D protein-ligand complex to a two-dimensional (2D) graph, and…

Biomolecules · Quantitative Biology 2022-10-31 Yiqiang Yi , Xu Wan , Kangfei Zhao , Le Ou-Yang , Peilin Zhao

The design of novel protein structures remains a challenge in protein engineering for applications across biomedicine and chemistry. In this line of work, a diffusion model over rigid bodies in 3D (referred to as frames) has shown success…

Machine Learning · Computer Science 2023-05-24 Jason Yim , Brian L. Trippe , Valentin De Bortoli , Emile Mathieu , Arnaud Doucet , Regina Barzilay , Tommi Jaakkola

Generative modeling of three-dimensional (3D) molecules is a fundamental yet challenging problem in drug discovery and materials science. Existing approaches typically represent molecules as 3D graphs and co-generate discrete atom types…

Machine Learning · Statistics 2026-03-16 Yuchen Hua , Xingang Peng , Jianzhu Ma , Muhan Zhang