GraphPBSP: Protein binding site prediction based on Graph Attention Network and pre-trained model ProstT5.

Journal: International journal of biological macromolecules
PMID:

Abstract

Protein-protein/peptide interactions play crucial roles in various biological processes. Exploring their interactions attracts wide attention. However, accurately predicting their binding sites remains a challenging task. Here, we develop an effective model GraphPBSP based on Graph Attention Network with Convolutional Neural Network and Multilayer Perceptron for protein-protein/peptide binding site prediction, which utilizes various feature types derived from protein sequence and structure including interface residue pairwise propensity developed by us and sequence embeddings obtained from a new pre-trained model ProstT5, alongside physicochemical properties and structural features. To our best knowledge, ProstT5 sequence embeddings and residue pairwise propensity are first introduced for protein-protein/peptide binding site prediction. Additionally, we propose a spatial neighbor-based feature statistic method for effectively considering key spatially neighboring information that significantly improves the model's prediction ability. For model training, a multi-scale objective function is constructed, which enhances the learning capability across samples of the same or different classes. On multiple protein-protein/peptide binding site test sets, GraphPBSP outperforms the currently available state-of-the-art methods with an excellent performance. Additionally, its performances on protein-DNA/RNA binding site test sets also demonstrate its good generalization ability. In conclusion, GraphPBSP is a promising method, which can offer valuable information for protein engineering and drug design.

Authors

  • Xiaohan Sun
    School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.
  • Zhixiang Wu
    College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.
  • Jingjie Su
    College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.
  • Chunhua Li
    School of Computer Science and Technology, Soochow University, Suzhou 215006, China.