SCREEN: A Graph-based Contrastive Learning Tool to Infer Catalytic Residues and Assess Enzyme Mutations.

Journal: Genomics, proteomics & bioinformatics
PMID: 39724324

Abstract

The accurate identification of catalytic residues contributes to our understanding of enzyme functions in biological processes and pathways. The increasing number of protein sequences necessitates computational tools for the automated prediction of catalytic residues in enzymes. Here, we introduce SCREEN, a graph neural network for the high-throughput prediction of catalytic residues via the integration of enzyme functional and structural information. SCREEN constructs residue representations based on spatial arrangements and incorporates enzyme function priors into such representations through contrastive learning. We demonstrate that SCREEN (1) consistently outperforms currently-available predictors; (2) provides accurate results when applied to inferred enzyme structures; and (3) generalizes well to enzymes dissimilar from those in the training set. We also show that the putative catalytic residues predicted by SCREEN mimic key structural and biophysical characteristics of native catalytic residues. Moreover, using experimental datasets, we show that SCREEN's predictions can be used to distinguish residues with a high mutation tolerance from those likely to cause functional loss when mutated, indicating that this tool might be used to infer disease-associated mutations. SCREEN is publicly available at https://github.com/BioColLab/SCREEN and https://ngdc.cncb.ac.cn/biocode/tool/7580.

Authors

  • Tong Pan
    Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia.
  • Yue Bi
    Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia.
  • Xiaoyu Wang
    Department of Statistics Florida State University Tallahassee, FL, USA.
  • Ying Zhang
    Department of Nephrology, Nanchong Central Hospital Affiliated to North Sichuan Medical College, Nanchong, China.
  • Geoffrey I Webb
    College of Information Engineering, Northwest A&F University, Yangling 712100, China, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia, National Engineering Laboratory for Industrial Enzymes and Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China, Centre for Research in Intelligent Systems, Faculty of Information Technology, Monash University, Melbourne, VIC 3800, Australia and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, VIC 3800, Australia.
  • Robin B Gasser
    Department of Veterinary Biosciences, Melbourne Veterinary School, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Lukasz Kurgan
    Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA.
  • Jiangning Song
    College of Information Engineering, Northwest A&F University, Yangling 712100, China, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia, National Engineering Laboratory for Industrial Enzymes and Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China, Centre for Research in Intelligent Systems, Faculty of Information Technology, Monash University, Melbourne, VIC 3800, Australia and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, VIC 3800, Australia College of Information Engineering, Northwest A&F University, Yangling 712100, China, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia, National Engineering Laboratory for Industrial Enzymes and Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China, Centre for Research in Intelligent Systems, Faculty of Information Technology, Monash University, Melbourne, VIC 3800, Australia and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, VIC 3800, Australia College of Information Engineering, Northwest A&F University, Yangling 712100, China, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia, National Engineering Laboratory for Industrial Enzymes and Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China, Centre for Research in Intelligent Systems, Faculty of Information Technology, Monash University, Melbourne, VIC 3800, Australia and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, VIC 3800, Australia.

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