Knowledge-aware contrastive heterogeneous molecular graph learning

Abstract

Molecular representation learning is pivotal in predicting molecular properties and advancing drug design. Traditional methodologies, which predominantly rely on homogeneous graph encoding, are limited by their inability to integrate external knowledge and represent molecular structures across different levels of granularity. To address these limitations, we propose a paradigm shift by encoding molecular graphs into heterogeneous structures, introducing a novel framework: Knowledge-aware Contrastive Heterogeneous Molecular Graph Learning. This approach leverages contrastive learning to enrich molecular representations with embedded external knowledge. KCHML conceptualizes molecules through three distinct graph views—molecular, elemental, and pharmacological—enhanced by heterogeneous molecular graphs and a dual message-passing mechanism. This design offers a comprehensive representation for property prediction, as well as for downstream tasks such as drug-drug interaction prediction. Extensive benchmarking demonstrates KCHML’s superiority over state-of-the-art molecular property prediction models, underscoring its ability to capture intricate molecular features.