PocketAnchor: Learning structure-based pocket representations for protein-ligand interaction prediction.

Abstract

Protein-ligand interactions are essential for cellular activities and drug discovery processes. Appropriately and effectively representing protein features is of vital importance for developing computational approaches, especially data-driven methods, for predicting protein-ligand interactions. However, existing approaches may not fully investigate the features of the ligand-occupying regions in the protein pockets. Here, we design a structure-based protein representation method, named PocketAnchor, for capturing the local environmental and spatial features of protein pockets to facilitate protein-ligand interaction-related learning tasks. We define "anchors" as probe points reaching into the cavities and those located near the surface of proteins, and we design a specific message passing strategy for gathering local information from the atoms and surface neighboring these anchors. Comprehensive evaluation of our method demonstrated its successful applications in pocket detection and binding affinity prediction, which indicated that our anchor-based approach can provide effective protein feature representations for improving the prediction of protein-ligand interactions.