基于分子对接技术虚拟筛选天然产物抗MRSA活性成分

Virtual Screening of Active Ingredients of Natural Products against Methicillin-Resistant Staphylococcus Aureus

目的基于分子对接技术从已经报道的具有抗菌和抑菌作用的天然产物中筛选出可能具有抗耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphy lococcus aureus,MRSA)的药物。方法收集具有现已经报道的抗菌或者抑菌作用的天然产物859个。选择PBP2a蛋白3D结构(PDB ID:3ZG0,2.60?),应用Discovery Studio 4.5(DS 4.5)软件的CDOCKER模块进行分子对接,再以原配体打分值为参考开展系统筛选研究,最后进行了分子的ADMET分析,筛选出具有新药开发前景的化合物。结果在PBP2a蛋白的变构位点和活性位点,打分值均高于原配体的候选化合物共计24个,其中ADMET比较好的化合物有9个。结论本研究筛选出来的Abyssinone V、Gancaonin C、Glycycoumarin、Isogancaonin C、Kuwanon A、Lupiwighteone、Quercetin-3-methyl ether、Rhamnazin、Wighteone等9个化合物已经有抗菌或抑菌作用的报道,但是至今为止还未进行过抗MRSA方面的研究,希望本研究能够为新药研发提供参考。

Objective Screen the natural products with antibacterial activity in order to find compounds against methicillin-resistant staphylococcus aureus using molecular docking technology.Methods 859 natural products with antibacterial or bacteriostatic effects that have been reported were collected.The 3 D structure of PBP2 a protein(PDB ID:3 ZG0,2.60?)was selected,and the CDOCKER module of Discovery Studio 4.5(DS4.5)software was used for molecular docking.Then the system screening study was carried out with the reference value of the original ligand,and finally the molecule was carried out.The ADMET analysis screens out compounds with prospects for new drug development.Results In the allosteric sites and active sites of PBP2 a protein,there were 24 candidate compounds with higher the scores than the original ligand,and 9 compounds with good ADMET.Conclusion Abyssinone V,Gancaonin C,Glycycoumarin,Isogancaonin C,Kuwanon A,Lupiwighteone,Quercetin-3-methyl ether,Rhamnazin and Wighteone had been reported to have antibacterial or antibacterial effects,but so far no research on anti-MRSA has been conducted.It is hoped to provide reference for the development of new drugs.