乙酰胆碱酯酶与抑制剂分子对接的ABEEMσπ/MM研究

Study on interaction of AChE and its ligands by ABEEMσπ/MM method

应用ABEEMσπ/MM方法,对乙酰胆碱酯酶抑制剂Tacrine(塔克宁)与组胺转甲基酶进行了分子对接.然后对乙酰胆碱酯酶与4种乙酰胆碱酯酶抑制剂的分子对接进行了研究.在研究中将受体分子固定,配体分子可自由移动,采用半柔性对接方式.通过对4种乙酰胆碱酯酶抑制剂与乙酰胆碱酯酶结合能大小的计算,得到结合能力大小顺序依次为:Donpezil(多奈哌齐)>Huperzine(石杉碱甲)>Rivastigmine(利发斯的明)>Tacrine(塔克宁).这个顺序与实验中得到的乙酰胆碱酯酶(AChE)抑制活性IC50值大小顺序相一致.为使用该方法进行抑制剂设计提供参考.

By means of atom-bond electronegativity equalization,investigation of the molecular dockings between acetylcholinesterase inhibitors（AChEI） Tacrine and histamine methyltransfrease was carried out.And then,the interaction of cholinesterase（AChE） and four kinds of cholinesterase inhibitors was studied.We fixed the receptor molecule,supposing that ligand molecule can move freely,and used the semi-flexible docking studies.The binding energies between four ACHEI and ACHE were calculated and the order of the binding capacity is：Donpezil〉Huperzine〉Rivastigmine〉Tacrine,which is in fair agreement with the experimental values of the acetylcholinesterase（AChE） inhibitory activity IC50.