GIaNt: Protein-Ligand Binding Affinity Prediction via Geometry-Aware Interactive Graph Neural Network

Drug discovery often relies on the successful prediction of protein-ligand binding affinity. Recent advances have shown great promise in applying graph neural networks (GNNs) for better affinity prediction by learning the representations of protein-ligand complexes. However, existing solutions usually treat protein-ligand complexes as topological graph data, thus the 3D geometry-based biomolecular structural information is not fully utilized. The essential intermolecular interactions with long-range dependencies, including type-wise interactions and molecule-wise interactions, are also neglected in GNN models. To this end, we propose a geometry-aware interactive graph neural network (GIaNt) which consists of two components: 3D geometric graph learning network (3DG-Net) and pairwise interactive learning network (Pi-Net). Specifically, 3DG-Net iteratively performs the node-edge interaction process to update embeddings of nodes and edges in a unified framework while preserving the 3D geometric factors among atoms, including spatial distance, polar angle and dihedral angle information in 3D space. Moreover, Pi-Net is adopted to incorporate both element type-level and molecule-level interactions. Specially, interactive edges are gathered with a subsequent reconstruction loss to reflect the global type-level interactions. Meanwhile, a pairwise attentive pooling scheme is designed to identify the critical interactive atoms for complex representation learning from a semantic view. An exhaustive experimental study on two benchmarks verifies the superiority of GIaNt.