ProAffinity-GNN: a novel approach to structure-based protein-protein binding affinity prediction via a curated data set and graph neural networks

Abstract

Protein-protein interactions (PPIs) are crucial for understanding biological processes and disease mechanisms, contributing significantly to advances in protein engineering and drug discovery. The accurate determination of binding affinities, essential for decoding PPIs, faces challenges due to the substantial time and financial costs involved in experimental and theoretical methods. This situation underscores the urgent need for more effective and precise methodologies for predicting binding affinity. Despite the abundance of research on PPI modeling, the field of quantitative binding affinity prediction remains underexplored, mainly due to a lack of comprehensive data. This study seeks to address these needs by manually curating pairwise interaction labels on available 3D structures of protein complexes, with experimentally determined binding affinities, creating the largest data set for structure-based pairwise protein interaction with binding affinity to date. Subsequently, we introduce ProAffinity-GNN, a novel deep learning framework using protein language model and graph neural network (GNN) to improve the accuracy of prediction of structure-based protein-protein binding affinities. The evaluation results across several benchmark test sets and an additional case study demonstrate that ProAffinity-GNN not only outperforms existing models in terms of accuracy but also shows strong generalization capabilities.