Abstract
MOTIVATION: Proteins are responsible for most biological functions, many of which require the interaction of more than one protein molecule. However, accurately predicting protein-protein interaction (PPI) sites (the interfacial residues of a protein that interact with other protein molecules) remains a challenge. The growing demand and cost associated with the reliable identification of PPI sites using conventional experimental methods call for computational tools for automated prediction and understanding of PPIs. RESULTS: We present Pair-EGRET, an edge-aggregated graph attention network that leverages the features extracted from pretrained transformer-like models to accurately predict PPI sites. Pair-EGRET works on a k-nearest neighbor graph, representing the 3D structure of a protein, and utilizes the cross-attention mechanism for accurate identification of interfacial residues of a pair of proteins. Through an extensive evaluation study using a diverse array of experimental data, evaluation metrics, and case studies on representative protein sequences, we demonstrate that Pair-EGRET can achieve remarkable performance in predicting PPI sites. Moreover, Pair-EGRET can provide interpretable insights from the learned cross-attention matrix. AVAILABILITY AND IMPLEMENTATION: Pair-EGRET is freely available in open source form at the GitHub Repository https://github.com/1705004/Pair-EGRET.