Enhancing drug property prediction with dual-channel transfer learning based on molecular fragment.

ABSTRACT

BACKGROUND: Accurate prediction of molecular property holds significance in contemporary drug discovery and medical research. Recent advances in AI-driven molecular property prediction have shown promising results. Due to the costly annotation of in vitro and in vivo experiments, transfer learning paradigm has been gaining momentum in extracting general self-supervised information to facilitate neural network learning. However, prior pretraining strategies have overlooked the necessity of explicitly incorporating domain knowledge, especially the molecular fragments, into model design, resulting in the under-exploration of the molecular semantic space. RESULTS: We propose an effective model with FRagment-based dual-channEL pretraining (FREL). Equipped with molecular fragments, FREL comprehensively employs masked autoencoder and contrastive learning to learn intra- and inter-molecule agreement, respectively. We further conduct extensive experiments on ten public datasets to demonstrate its superiority over state-of-the-art models. Further investigations and interpretations manifest the underlying relationship between molecular representations and molecular properties. CONCLUSIONS: Our proposed model FREL achieves state-of-the-art performance on the benchmark datasets, emphasizing the importance of incorporating molecular fragments into model design. The expressiveness of learned molecular representations is also investigated by visualization and correlation analysis. Case studies indicate that the learned molecular representations better capture the drug property variation and fragment semantics.