biostudies-literatureAtz KSwiss National Science FoundationScholarship Fund of the Swiss Chemical Industry3408https://www.ebi.ac.uk/biostudies/studies/S-EPMC11035696biostudies-literatureUnknown15(1)De novo drug design aims to generate molecules from scratch that possess specific chemical and pharmacological properties. We present a computational approach utilizing interactome-based deep learning for ligand- and structure-based generation of drug-like molecules. This method capitalizes on the unique strengths of both graph neural networks and chemical language models, offering an alternative to the need for application-specific reinforcement, transfer, or few-shot learning. It enables the "zero-shot" construction of compound libraries tailored to possess specific bioactivity, synthesizability, and structural novelty. In order to proactively evaluate the deep interactome learning framework for protein structure-based drug design, potential new ligands targeting the binding site of the Nature communicationsProspective de novo drug design with deep interactome learning.PMC11035696202245CRSII5_202245205321182176Hiss JAGrether UIff MHilleke MNippa DFSchiebroek CCGFocht DRomeo VIsert CSchneider PLedergerber JHakansson MKuhn BSchneider GAtz KCotos LMerk DfalseProspective de novo drug design with deep interactome learning.De novo drug design aims to generate molecules from scratch that possess specific chemical and pharmacological properties. We present a computational approach utilizing interactome-based deep learning for ligand- and structure-based generation of drug-like molecules. This method capitalizes on the unique strengths of both graph neural networks and chemical language models, offering an alternative to the need for application-specific reinforcement, transfer, or few-shot learning. It enables the "zero-shot" construction of compound libraries tailored to possess specific bioactivity, synthesizability, and structural novelty. In order to proactively evaluate the deep interactome learning framework for protein structure-based drug design, potential new ligands targeting the binding site of the 2024-01-01T00:00:00Z2024 Apr2026-06-01T19:59:22.189Z2025-08-17T03:06:08.357ZS-EPMC110356963864935110.1038/s41467-024-47613-w