基于分子对接虚拟筛选PBP2a蛋白蒲公英活性成分抗菌剂  

Virtual screening of PBP2a protein inhibitors from active components of dandelion based on molecular docking

作　　者：刘旭 吕小刚 梁引库[1,2] 穆阿宁 LIU Xu;LYU Xiao-gang;LIANG Yin-ku;Mu A-ning(School of Bioscience and Engineering,Shaanxi University of Technology,Hanzhong 723000,China;Shaanxi Key Laboratory of Bio-resources,Hanzhong 723000,China)

机构地区：[1]陕西理工大学生物科学与工程学院,陕西汉中723000 [2]陕西省资源生物重点实验室,陕西汉中723000

出　　处：《陕西理工大学学报（自然科学版）》2021年第5期71-79,共9页Journal of Shaanxi University of Technology:Natural Science Edition

基　　金：秦巴生物资源与生态环境国培重点实验室项目(SLGPT2019KF04-05);陕西省资源生物重点实验室项目(AZA-15-03)。

摘　　要：青霉素结合蛋白PBP2a是使耐甲氧西林金黄色葡萄球菌(MRSA)产生耐药的原因之一,基于该靶点的中药成分虚拟筛选有助于发现中药在治疗细菌耐药的有效物质,因此基于分子对接技术从蒲公英中筛选出可能抗MRSA的天然药物,并初步探讨所筛选活性化合物与PBP2a蛋白相互作用机制。选择PBP2a蛋白3D结构(PDB ID:5M19),用Autodock vina进行分子对接,以原配体苯唑西林打分值为参考进行筛选,在PBP2a蛋白活性位点处,打分值高于原配体的候选化合物共计57个。其中,蒲公英甾醇、异绿原酸A、款冬二醇、羽扇豆醇、齐墩果酸对PBP2a蛋白有较好的结合作用。这5种物质都与ARG151、ARG241氨基酸残基形成氢键作用,且异绿原酸A和齐墩果酸报道有增敏和抑菌作用。实验结果可以为发现新型抗菌药提供理论基础。Penicillin binding protein PBP2a is one of the reasons for the drug resistance of methicillin resistant Staphylococcus aureus(MRSA).The virtual screening of traditional Chinese medicine components based on this target is helpful to find the effective substances of traditional Chinese medicine in the treatment of bacterial drug resistance.Therefore,the natural drugs that may resist MRSA are screened from dandelion based on molecular docking technology,the interaction mechanism between the screened active compounds and PBP2a protein is discussed.The 3D structure of PBP2a protein(PDB ID:5M19)has been selected,and the molecular docking has been carried out with autodock Vina.The scoring value of the original ligand oxacillin sodium has been used as a reference for screening.At the active site of PBP2a protein,there are 57 candidate compounds which scoring value are higher than that of the original ligand.Among them,dandelion sterol,isochlorogenic acid,asparagus diol,Lupin alcohol and oleanolic acid have a good binding effect on PBP2a protein.Those all form hydrogen bonds with ARG151 and ARG241.Moreover,isochlorogenic acid A and oleanolic acid are reported to have sensitizing and antibacterial effects which can provide a theoretical basis for the discovery of new antibiotics.

关 键 词：分子对接 耐甲氧西林金黄色葡萄球菌 中药筛选 青霉素结合蛋白 

分 类 号：R93[医药卫生—生药学]