Sequence-based machine learning method for predicting the effects of phosphorylation on protein-protein interactions.

Journal: International journal of biological macromolecules
PMID:

Abstract

Protein phosphorylation, catalyzed by kinases, is an important biochemical process, which plays an essential role in multiple cell signaling pathways. Meanwhile, protein-protein interactions (PPI) constitute the signaling pathways. Abnormal phosphorylation status on protein can regulate protein functions through PPI to evoke severe diseases, such as Cancer and Alzheimer's disease. Due to the limited experimental evidence and high costs to experimentally identify novel evidence of phosphorylation regulation on PPI, it is necessary to develop a high-accuracy and user-friendly artificial intelligence method to predict phosphorylation effect on PPI. Here, we proposed a novel sequence-based machine learning method named PhosPPI, which achieved better identification performance (Accuracy and AUC) than other competing predictive methods of Betts, HawkDock and FoldX. PhosPPI is now freely available in web server (https://phosppi.sjtu.edu.cn/). This tool can help the user to identify functional phosphorylation sites affecting PPI and explore phosphorylation-associated disease mechanism and drug development.

Authors

  • Xiaokun Hong
    State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
  • Jiyang Lv
    State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
  • Zhengxin Li
    State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
  • Yi Xiong
    Departement of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, China.
  • Jian Zhang
    College of Pharmacy, Ningxia Medical University, Yinchuan, NingxiaHui Autonomous Region, China.
  • Hai-Feng Chen
    State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai200240, China.