$\mathcal{O}$-GNN: incorporating ring priors into molecular modeling

Abstract

Cyclic compounds that contain at least one ring play an important role in drug design. Despite the recent success of molecular modeling with graph neural networks (GNNs), few models explicitly take rings in compounds into consideration, consequently limiting the expressiveness of the models. In this work, we design a new variant of GNN, ring-enhanced GNN ($\mathcal{O}$-GNN), that explicitly models rings in addition to atoms and bonds in compounds. In $\mathcal{O}$-GNN, each ring is represented by a latent vector, which contributes to and is iteratively updated by atom and bond representations. Theoretical analysis shows that $\mathcal{O}$-GNN is able to distinguish two isomorphic subgraphs lying on different rings using only one layer while conventional graph convolutional neural networks require multiple layers to distinguish, demonstrating that $\mathcal{O}$-GNN is more expressive. Through experiments, $\mathcal{O}$-GNN shows good performance on $\bf{11}$ public datasets. In particular, it achieves state-of-the-art validation result on the PCQM4Mv1 benchmark (outperforming the previous KDDCup champion solution) and the drug-drug interaction prediction task on DrugBank. Furthermore, $\mathcal{O}$-GNN outperforms strong baselines (without modeling rings) on the molecular property prediction and retrosynthesis prediction tasks.