DECOMPDIFF: Diffusion Models with Decomposed Priors for Structure-Based Drug Design

Jiaqi Guan, Xiangxin Zhou, Yuwei Yang, Yu Bao, Jian Peng, Jianzhu Ma, Qiang Liu, Liang Wang, Quanquan Gu

Research output: Contribution to journalConference articlepeer-review


Designing 3D ligands within a target binding site is a fundamental task in drug discovery. Existing structured-based drug design methods treat all ligand atoms equally, which ignores different roles of atoms in the ligand for drug design and can be less efficient for exploring the large drug-like molecule space. In this paper, inspired by the convention in pharmaceutical practice, we decompose the ligand molecule into two parts, namely arms and scaffold, and propose a new diffusion model, DECOMPDIFF, with decomposed priors over arms and scaffold. In order to facilitate the decomposed generation and improve the properties of the generated molecules, we incorporate both bond diffusion in the model and additional validity guidance in the sampling phase. Extensive experiments on CrossDocked2020 show that our approach achieves state-of-the-art performance in generating high-affinity molecules while maintaining proper molecular properties and conformational stability, with up to -8.39 Avg. Vina Dock score and 24.5% Success Rate. The code is provided at

Original languageEnglish (US)
Pages (from-to)11827-11846
Number of pages20
JournalProceedings of Machine Learning Research
StatePublished - 2023
Externally publishedYes
Event40th International Conference on Machine Learning, ICML 2023 - Honolulu, United States
Duration: Jul 23 2023Jul 29 2023

ASJC Scopus subject areas

  • Artificial Intelligence
  • Software
  • Control and Systems Engineering
  • Statistics and Probability


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