SCMBYK: prediction and characterization of bacterial tyrosine-kinases based on propensity scores of dipeptides

BMC Bioinformatics

Research

Tamara Vasylenko¹  Yi-Fan Liou¹  Hsiao-Wei Chu¹  Yu-Ling Chou¹  Yung-Sung Lai¹  Po-Chin Chiou¹  Shinn-Ying Ho²  Hui-Ling Huang² 

[1] Institute of Bioinformatics and Systems Biology, National Chiao Tung University, 300, Hsinchu, Taiwan;Institute of Bioinformatics and Systems Biology, National Chiao Tung University, 300, Hsinchu, Taiwan;College of Biological Science and Technology, National Chiao Tung University, 300, Hsinchu, Taiwan;Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, Taiwan;

关键词: BY-kinase;    Scoring card method;    Drug repurposing;    Propensity scores;    Dipeptide;   

DOI  :  10.1186/s12859-016-1371-4

来源: Springer

【 摘 要 】

BackgroundBacterial tyrosine-kinases (BY-kinases), which play an important role in numerous cellular processes, are characterized as a separate class of enzymes and share no structural similarity with their eukaryotic counterparts. However, in silico methods for predicting BY-kinases have not been developed yet. Since these enzymes are involved in key regulatory processes, and are promising targets for anti-bacterial drug design, it is desirable to develop a simple and easily interpretable predictor to gain new insights into bacterial tyrosine phosphorylation. This study proposes a novel SCMBYK method for predicting and characterizing BY-kinases.ResultsA dataset consisting of 797 BY-kinases and 783 non-BY-kinases was established to design the SCMBYK predictor, which achieved training and test accuracies of 97.55 and 96.73%, respectively. Furthermore, the leave-one-phylum-out method was used to predict specific bacterial phyla hosts of target sequences, gaining 97.39% average test accuracy. After analyzing SCMBYK-derived propensity scores, four characteristics of BY-kinases were determined: 1) BY-kinases tend to be composed of α-helices; 2) the amino-acid content of extracellular regions of BY-kinases is expected to be dominated by residues such as Val, Ile, Phe and Tyr; 3) BY-kinases structurally resemble nuclear proteins; 4) different domains play different roles in triggering BY-kinase activity.ConclusionsThe SCMBYK predictor is an effective method for identification of possible BY-kinases. Furthermore, it can be used as a part of a novel drug repurposing method, which recognizes putative BY-kinases and matches them to approved drugs. Among other results, our analysis revealed that azathioprine could suppress the virulence of M. tuberculosis, and thus be considered as a potential antibiotic for tuberculosis treatment.

【 授权许可】

CC BY   
© The Author(s). 2016