分子模拟研究1,3,4-噻二唑类衍生物对AChE/BChE的生物活性和选择性机理  

Studies on Mechanism of Bioactivity and Selectivity of 1,3,4-Thiadiazol Inhibitors to AChE/BChE by Molecular Dynamic

作　　者：赵腾腾 杨雪雨 王亚莉 朱小蕾 Zhao Tengteng;Yang Xueyu;Wang Yali;Zhu Xiaolei(State Key Laboratory of Materials-Oriented Chemical Engineering,College of Chemical Engineering,Nanjing Tech University,Nanjing 210009,China)

机构地区：[1]南京工业大学化工学院,材料化学工程国家重点实验室,江苏南京210009

出　　处：《南京师大学报（自然科学版）》2018年第1期55-60,共6页Journal of Nanjing Normal University(Natural Science Edition)

基　　金：国家自然科学基金项目(20706029、20876073、91434109).

摘　　要：乙酰胆碱酯酶(ACh E)和丁酰胆碱酯酶(BCh E)均属于胆碱酯酶类(Ch Es),具有不同的催化特性及抑制模式,是具有高度同源性的两种蛋白质,在神经系统中发挥着重要的作用.揭示胆碱酯酶抑制剂的选择性机理是开发新型的阿尔茨海默症药物的重要课题.我们研究了3种1,3,4-噻二唑抑制剂对ACh E/BCh E的生物活性和选择性机理.采用MM-PBSA方法对3种抑制剂与ACh E/BCh E之间的相互作用能进行了计算.研究结果表明,3种抑制剂对ACh E均表现出较高的活性,说明这3种抑制剂能够选择性抑制ACh E,所得计算结合自由能排序与抑制剂的实验抑制常数吻合较好.Acetylcholinesterase(AChE)and butyrylcholinesterase(BChE)both belonging to the family of cholinesterases(ChEs),which differ in their catalytic properties and inhibition patterns,are highly homologous proteins and play important roles in the cholinergic nervous system.Revealing selectivity mechanism of inhibitors to cholinesterases is an important issue to develop potential Alzheimer's drugs.In current work,we investigate the bioactivity and selectivity of three 1,3,4-thiadiazol inhibitors to AChE/BChE.The binding interactions between the three inhibitors and AChE/BChE are examined based on the MM-PBSA method.The results demonstrate that three kinds of inhibitors show higher activity to AChE than BChE,and illustrate that the three inhibitors can inhibit AChE selectively.The rank of calculated binding free energies is in good agreement with experimental inhibiting constants of the three inhibitors.

关 键 词：胆碱酯酶 1 3 4-噻二唑类抑制剂 分子动力学模拟 MM-PBSA方法 选择性 

分 类 号：O643.1[理学—物理化学]