PREvaIL, an integrative approach for inferring catalytic residues using sequence, structural, and network features in a machine-learning framework. Determining the catalytic residues in an enzyme is critical to our understanding the relationship between protein sequence, structure, function, and enhancing our ability to design novel enzymes and their inhibitors. Although many enzymes have been sequenced, and their primary and tertiary structures determined, experimental methods for enzyme functional characterization lag behind. Because experimental methods used for identifying catalytic residues are resource- and labor-intensive, computational approaches have considerable value and are highly desirable for their ability to complement experimental studies in identifying catalytic residues and helping to bridge the sequence-structure-function gap. In this study, we describe a new computational method called PREvaIL for predicting enzyme catalytic residues. This method was developed by leveraging a comprehensive set of informative features extracted from multiple levels, including sequence, structure, and residue-contact network, in a random forest machine-learning framework. Extensive benchmarking experiments on eight different datasets based on 10-fold cross-validation and independent tests, as well as side-by-side performance comparisons with seven modern sequence- and structure-based methods, showed that PREvaIL achieved competitive predictive performance, with an area under the receiver operating characteristic curve and area under the precision-recall curve ranging from 0.896 to 0.973 and from 0.294 to 0.523, respectively. We demonstrated that this method was able to capture useful signals arising from different levels, leveraging such differential but useful types of features and allowing us to significantly improve the performance of catalytic residue prediction. We believe that this new method can be utilized as a valuable tool for both understanding the complex sequence-structure-function relationships of proteins and facilitating the characterization of novel enzymes lacking functional annotations.

References in zbMATH (referenced in 10 articles )

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  1. Ahmad, Jamal; Hayat, Maqsood: MFSC: multi-voting based feature selection for classification of Golgi proteins by adopting the general form of Chou’s PseAAC components (2019)
  2. Chen, Guodong; Cao, Man; Yu, Jialin; Guo, Xinyun; Shi, Shaoping: Prediction and functional analysis of prokaryote lysine acetylation site by incorporating six types of features into Chou’s general PseAAC (2019)
  3. Hussain, Waqar; Khan, Yaser Daanial; Rasool, Nouman; Khan, Sher Afzal; Chou, Kuo-Chen: SPrenylC-PseAAC: a sequence-based model developed via Chou’s 5-steps rule and general PseAAC for identifying S-prenylation sites in proteins (2019)
  4. Jia, Jianhua; Li, Xiaoyan; Qiu, Wangren; Xiao, Xuan; Chou, Kuo-Chen: iPPI-PseAAC(CGR): identify protein-protein interactions by incorporating chaos game representation into PseAAC (2019)
  5. Pan, Yi; Wang, Shiyuan; Zhang, Qi; Lu, Qianzi; Su, Dongqing; Zuo, Yongchun; Yang, Lei: Analysis and prediction of animal toxins by various Chou’s pseudo components and reduced amino acid compositions (2019)
  6. Cheng, Xiang; Xiao, Xuan; Chou, Kuo-Chen: pLoc_bal-mGneg: predict subcellular localization of Gram-negative bacterial proteins by quasi-balancing training dataset and general PseAAC (2018)
  7. Jia, Cangzhi; Yang, Qing; Zou, Quan: NucPosPred: predicting species-specific genomic nucleosome positioning via four different modes of general PseKNC (2018)
  8. Mei, Juan; Fu, Yi; Zhao, Ji: Analysis and prediction of ion channel inhibitors by using feature selection and Chou’s general pseudo amino acid composition (2018)
  9. Sabooh, M. Fazli; Iqbal, Nadeem; Khan, Mukhtaj; Khan, Muslim; Maqbool, H. F.: Identifying 5-methylcytosine sites in RNA sequence using composite encoding feature into Chou’s PseKNC (2018)
  10. Sankari, E. Siva; Manimegalai, D.: Predicting membrane protein types by incorporating a novel feature set into Chou’s general PseAAC (2018)