2024/10/28 by Xiangxin Zhou, Zhou, Xiangxin, Jiaqi Guan +9 · 3 citations
Engineering · Mathematics · #3D Printing in Biomedical Research #Biomolecules (q-bio.BM) #FOS: Biological sciences #FOS: Computer and information sciences #Innovative Microfluidic and Catalytic Techniques Innovation #Machine Learning (cs.LG) #Mathematical Biology Tumor Growth
paper · pdf · doi:10.48550/arxiv.2410.20688
openalex publication_date 2024/10/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Dual-target therapeutic strategies have become a compelling approach and attracted significant attention due to various benefits, such as their potential in overcoming drug resistance in cancer therapy. Considering the tremendous success that deep generative models have achieved in structure-based drug design in recent years, we formulate dual-target drug design as a generative task and curate a novel dataset of potential target pairs based on synergistic drug combinations. We propose to design dual-target drugs with diffusion models that are trained on single-target protein-ligand complex pairs. Specifically, we align two pockets in 3D space with protein-ligand binding priors and build two complex graphs with shared ligand nodes for SE(3)-equivariant composed message passing, based on which we derive a composed drift in both 3D and categorical probability space in the generative process. Our algorithm can well transfer the knowledge gained in single-target pretraining to dual-target scenarios in a zero-shot manner. We also repurpose linker design methods as strong baselines for this task. Extensive experiments demonstrate the effectiveness of our method compared with various baselines.