MVGNN-PPIS: A novel multi-view graph neural network for protein-protein interaction sites prediction based on...

Protein-protein interactions (PPI) are crucial for understanding numerous biological processes and pathogenic mechanisms. Identifying interaction sites is essential for biomedical research and targeted drug development. Compared to experimental methods, accurate computational approaches for protein-protein interaction sites (PPIS) prediction can save significant time and costs. In this study, we propose a novel model named MVGNN-PPIS. To the best of our knowledge, it is the first to utilize predicted structures generated by AlphaFold3, and combined with transfer learning techniques, for predicting PPIS. This approach addresses the limitations of traditional methods that depend on native protein structures and multiple sequence alignments (MSA). Additionally, we introduced a multi-view graph framework based on two types of graph structures: the k-nearest neighbor graph and the adjacency matrix. By alternately employing a Graph Transformer and Graph Convolutional Networks (GCN) to aggregate node information, this framework effectively captures both local and global dependencies of each residue in the predicted structures, thereby significantly enhancing the model's sensitivity to binding sites. This framework further integrates direction, distances and angular information between the 3D coordinates of side-chain atom centroids to construct a relative coordinate system, generating enhanced edge features that ensure the model's equivariance to molecular translations and rotations in space. During training, the Focal Loss function is employed to effectively address the class imbalance in the dataset. Experimental results demonstrate that MVGNN outperforms the current state-of-the-art methods across multiple PPIS benchmark datasets. To further validate the model's generalization capability, we extended MVGNN to the domain of predicting protein-nucleic acid interaction sites, where it also achieved superior performance.