基于分子对接的虚拟筛选发现磷酸乙醇胺甲基转移酶抑制剂

Virtual Screening of Phosphoethanolamine Methyltransferase, PEAMT Inhibitors Based on Molecular Docking

目的:运用分子对接从生物碱数据库中筛选具有磷酸乙醇胺甲基转移酶(phosphoethanolamine methyltransferase, PEAMT)抑制活性的成分。方法:以PEAMT为药物靶标,利用相似性筛选、分子对接技术、类药性评估等多轮筛选策略,从生物碱化合物数据库中挖掘命中分子,并运用AutoDock Vina、PyMOL及LigPlus软件探索命中分子与靶点蛋白的结合方式和亲和力。结果:通过相似性虚拟筛选,共获得100个小分子,进行分子对接保留了结合能低于阈值的5个分子,其中4个分子符合Lipinski’s Rule,分别为匹格列酮、5’-腺苷酸、异鸟苷和腺苷,其中吡格列酮和5’-腺苷酸与PEAMT具有较高的结合亲和力,且作用方式与原晶体复合物相似,为最佳命中分子。结论:相似性筛选和分子对接的虚拟筛选策略可为松材线虫PEAMT抑制剂的开发提供研究方向。

Objective: To screen the components with phosphoethanolamine methyltransferase (PEAMT) inhibitory activity from alkaloid database using molecular docking. Methods: The PEAMT was taken as the drug target, and multiple rounds of virtual screening strategies, such as similarity screening, molecular docking technology and drug-like evaluation, were used to explore the hit molecules from alkaloid compound database. AutoDock Vina, PyMOL and LigPlus software were used to explore the binding mode and affinity of the hit molecules with the target protein. Result: 100 small molecules were obtained through similarity virtual screening, and 5 molecules with binding energy lower than threshold were retained by molecular docking, 4 of them were in line with Lipinski’s Rule, including pioglitazone, 5’-adenylic acid, isoguanosine and adenosine, respectively. Pioglitazone and 5’-adenylate were the best hit molecules because of high binding affinity with PEAMT and similar modes of action to that of the original crystal complex. Conclusion: The virtual screening strategy of similarity screening and molecular docking can provide research direction for the development of Bursaphelenchus xylophilus PEAMT inhibitors.