Abstract
MOTIVATION: Predicting protein-protein interaction (PPI) sites is essential for advancing our understanding of protein interactions, as accurate predictions can significantly reduce experimental costs and time. While considerable progress has been made in identifying binding sites at the level of individual amino acid residues, the prediction accuracy for residue subsequences at transitional boundaries-such as those represented by patterns like singular structures (mutation characteristics of contiguous interacting-residue segments) or edge structures (boundary transitions between interacting/non-interacting residue segments) still requires improvement. RESULTS: we propose a novel PPI site prediction method named MVSO-PPIS. This method integrates two complementary feature extraction modules, a subgraph-based module and an enhanced graph attention module. The extracted features are fused using an attention-based fusion mechanism, producing a composite representation that captures both local protein substructures and global contextual dependencies. MVSO-PPIS is trained to jointly optimize three objectives: overall PPI site prediction accuracy, edge structural consistency, and recognition of unique structural patterns in PPI site sequences. Experimental results on benchmark datasets demonstrate that MVSO-PPIS outperforms existing baseline models in both accuracy and structural interpretability. AVAILABILITY AND IMPLEMENTATION: The datasets, source codes, and models of MVSO-PPIS are all available at https://github.com/Edwardblue282/MVSO-PPIS.