標題: | SCMBYK: prediction and characterization of bacterial tyrosine-kinases based on propensity scores of dipeptides |
作者: | Vasylenko, Tamara Liou, Yi-Fan Chiou, Po-Chin Chu, Hsiao-Wei Lai, Yung-Sung Chou, Yu-Ling Huang, Hui-Ling Ho, Shinn-Ying 生物科技學院 生物資訊及系統生物研究所 College of Biological Science and Technology Institude of Bioinformatics and Systems Biology |
關鍵字: | BY-kinase;Scoring card method;Drug repurposing;Propensity scores;Dipeptide |
公開日期: | 22-十二月-2016 |
摘要: | Background: Bacterial 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. Results: A 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 leaveone-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 a-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. Conclusions: The 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. |
URI: | http://dx.doi.org/10.1186/s12859-016-1371-4 http://hdl.handle.net/11536/134503 |
ISSN: | 1471-2105 |
DOI: | 10.1186/s12859-016-1371-4 |
期刊: | BMC BIOINFORMATICS |
Volume: | 17 |
顯示於類別: | 會議論文 |