Structure-aware protein-protein interaction site prediction using deep graph convolutional network.

MOTIVATION: Protein-protein interactions (PPI) play crucial roles in many biological processes, and identifying PPI sites is an important step for mechanistic understanding of diseases and design of novel drugs. Since experimental approaches for PPI site identification are expensive and time-consuming, many computational methods have been developed as screening tools. However, these methods are mostly based on neighbored features in sequence, and thus limited to capture spatial information. RESULTS: We propose a deep graph-based framework GraphPPIS (deep Graph convolutional network for Protein-Protein Interacting Site prediction) for PPI site prediction, where the PPI site prediction problem was converted into a graph node classification task and solved by deep learning using the initial residual and identity mapping techniques. We showed that a deeper architecture (up to 8 layers) allows significant performance improvement over other sequence-based and structure-based methods by more than 12.5% and 10.5% on AUPRC and MCC, respectively. Further analyses indicated that the predicted interacting sites by GraphPPIS are more spatially clustered and closer to the native ones even when false-positive predictions are made. The results highlight the importance of capturing spatially neighboring residues for interacting site prediction. AVAILABILITY: The datasets, the pre-computed features, and the source codes along with the pre-trained models of GraphPPIS are available at https://github.com/biomed-AI/GraphPPIS. The GraphPPIS web server is freely available at https://biomed.nscc-gz.cn/apps/GraphPPIS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.