基于泛基因组学和消减蛋白质组学技术筛选金黄色葡萄球菌新型抗菌靶点及其药物的分子对接分析

Molecular docking analysis on screening of novel antibacterial targets and their drugs of Staphylococcus aureus based on pan-genomics and subtractive proteomics techniques

摘要

目的 应用泛基因组学和消减蛋白质组学技术从金黄色葡萄球菌基因组中筛选新抗菌靶点，为抗金黄色葡萄球菌药物的研发奠定基础。 方法 在美国国家生物技术信息中心（NCBI）数据库中以金黄色葡萄球菌为关键词检索全基因组测序数据，收集50个测序级别为Complete的菌株基因组数据。采用BPGA工具对基因组数据进行泛基因组分析获得金黄色葡萄球菌核心基因，采用消减蛋白质组学技术从中筛选获得潜在抗菌靶点，以潜在抗菌靶点为受体，采用LibDock软件从美国食品药品监督管理局（FDA）批准的药物库中筛选潜在的抗金黄色葡萄球菌药物，并采用分子对接技术分析药物和靶点的结合能力。 结果 50 个金黄色葡萄球菌基因组中共有 14 379 个基因家族，其中1 620 个为核心基因。消减蛋白质组学分析，酪氨酸自激酶 1335 为潜在的抗金黄色葡萄球菌靶点。采用LibDock软件筛选出巴龙霉素、替诺福韦二吡呋酯和阿德福韦等9个化合物可能针对该靶点蛋白发挥抗金黄色葡萄球菌作用，分子对接结果显示靶点与化合物结合力良好。 结论 酪氨酸自激酶可能是一种抗金黄色葡萄球菌潜在的靶点。

Abstract

Objective To use pan-genomics and subtractive proteomics techniques to screen the new antibacterial targets from the Staphylococcus aureus genome， and to lay the foundation for the development of anti-Staphylococcus aureus drugs. Methods The genome sequencing data of 50 strains with sequencing level Complete were collected by searching the whole genome sequencing data in the National Center for Biotechnology Information （NCBI） Database with Staphylococcus aureus as the keyword；BPGA tool was used to conduct the pan-genomics analysis on the genomic data to obtain the core genes of Staphylococcus aureus； subtractive proteomics technique was used to screen the potential antibacterial targets from the core genes. These potential antibacterial targets were used as the receptors； LibDock software was used to screen the potential anti-Staphylococcus aureus drugs from the US Food and Drug Administration （FDA）-approved drug library； molecular docking technology was used to analyze the binding abilities of the drugs and targets. Results There were 14 379 gene families in the 50 Staphylococcus aureus genomes， of which 1 620 were the core genes. The subtractive proteomics analysis results showed that tyrosine autokinase 1335 was the potential anti-Staphylococcus aureus target. LibDock software screened out nine compounds， including balofloxacin， tenofovir disoproxil fumarate， and adefovir， that may exert anti-Staphylococcus aureus effects on this target protein. The molecular docking results showed there was good binding abilities between the targets and the compounds. Conclusion Tyrosine autokinase may be the potential target for anti-Staphylococcus aureus.

关键词

金黄色葡萄菌 / 泛基因组 / 分子对接 / 消减蛋白质组

Key words

Staphylococcus aureus / Pan-genome / Molecular docking / Subtractive proteome

Author summay

谭锦莉 （1995-），女，广东省广州市人，在读硕士研究生，主要从事病原生物学方面的研究。