Interface-aware molecular generative framework for protein-protein interaction modulators.

ABSTRACT: Protein-protein interactions (PPIs) play a crucial role in numerous biochemical and biological processes. Although several structure-based molecular generative models have been developed, PPI interfaces and compounds targeting PPIs exhibit distinct physicochemical properties compared to traditional binding pockets and small-molecule drugs. As a result, generating compounds that effectively target PPIs, particularly by considering PPI complexes or interface hotspot residues, remains a significant challenge. In this work, we constructed a comprehensive dataset of PPI interfaces with active and inactive compound pairs. Based on this, we propose a novel molecular generative framework tailored to PPI interfaces, named GENiPPI. Our evaluation demonstrates that GENiPPI captures the implicit relat

SUBMITTER: Wang J 

PROVIDER: S-EPMC11662471 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature