Comparative genomics study for identification of drug and vaccine targets in Vibrio cholerae: MurA ligase as a case study.

• 影响指数: 4.31
• 发表时间: Jan 2014
• 来源期刊: Genomics
• DOI: 10.1016/j.ygeno.2013.12.002
• PMID: 24368230
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 生物
• 作者列表: Chawley P,Samal HB,Prava J,Suar M,Mahapatra RK

关键词: Antibiotics; Comparative genomics; Metabolic pathways; MurA; V. cholerae

Mesh: Alkyl and Aryl Transferases / genetics metabolism; Amino Acid Sequence; Bacterial Proteins / genetics metabolism; Comparative Genomic Hybridization; Computational Biology; Drug Delivery Systems / methods; Drug Design; Humans; Ligases / genetics metabolism; Lipopolysaccharides / biosynthesis; Metabolic Networks and Pathways / genetics; Molecular Sequence Data; Peptidoglycan / biosynthesis; Protein Conformation; Proteomics; Vaccines / chemistry; Vibrio cholerae / drug effects enzymology

Abstract

A systematic workflow consisting of comparative genomics, metabolic pathways analysis and additional drug prioritization parameters identified 264 proteins of Vibrio cholerae which were predicted to be absent in Homo sapiens. Among these, 40 proteins were identified as essential proteins that could serve as potential drug and vaccine targets. Additional prioritization parameters characterized 11 proteins as vaccine candidates while druggability of each of the identified proteins as evaluated by the Drug Bank database which prioritized 16 proteins suitable for drug targets. As a case study, we built a homology model of one of the potential drug targets, MurA ligase, using MODELLER (9v12) software. The model has been further explored for in silico docking with inhibitors having druggability potential from the Drug Bank database. Results from this study could facilitate selecting V. cholerae proteins for drug design and vaccine production pipelines in future.