FuncPhos-STR: An integrated deep neural network for functional phosphosite prediction based on AlphaFold protein structure and dynamics

Abstract

Phosphorylation modifications play important regulatory roles in most biological processes. However, the functional assignment for the vast majority of the identified phosphosites remains a major challenge. Here, we provide a deep learning framework named FuncPhos-STR as an online resource, for functional prediction and structural visualization of human proteome-level phosphosites. Based on our reported FuncPhos-SEQ framework, which was built by integrating phosphosite sequence evolution and protein-protein interaction (PPI) information, FuncPhos-STR was developed by further integrating the structural and dynamics information on AlphaFold protein structures. The characterized structural topology and dynamics features underlying functional phosphosites emphasized their molecular mechanism for regulating protein functions. By integrating the structural and dynamics, sequence evolutionary, and PPI network features from protein different dimensions, FuncPhos-STR has advantage over other reported models, with the best AUC value of 0.855. Using FuncPhos-STR, the phosphosites inside the pocket regions are accessible to higher functional scores, theoretically supporting their potential regulatory mechanism. Overall, FuncPhos-STR would accelerate the functional identification of huge unexplored phosphosites, and facilitate the elucidation of their allosteric regulation mechanisms. The web server of FuncPhos-STR is freely available at http://funcptm.jysw.suda.edu.cn/str.