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目的：研究胆碱酯酶水解机制和有机磷酸酯对胆碱酯酶的中毒、老化和重活化机制，为新重活化剂的分子设计提供理论依据。方法：参考半经验量子化学ＰＭ３方法对电鳐乙酰胆碱酯酶活性中心与乙酰胆碱相互作用的计算机模拟研究结果，在预测人脑乙酰胆碱酯酶三维空间结构的基础上，采用对接（ｄｏｃｋｉｎｇ）技术模拟研究乙酰胆碱、４种有机磷酸酯与乙酰胆碱酯酶活性中心在三维空间结构上的分子间相互作用。结果：乙酰胆碱与胆碱酯酶活性中心的色氨酸有比较好的对接关系，与谷氨酸距离较远；４种神经性毒剂在胆碱酯酶活性中心的对接情况各不相同，并且其毒性与催化三元体的距离成反比、与静电作用大小成正比。结论：胆碱酯酶催化三元体可能由丝氨酸、组氨酸和色氨酸组成，谷氨酸在促进质子转移过程中是不可缺少的；中毒和老化都可能存在一系列过程，老化酶形成的初期阶段也可能被重活化，并预测了增加初期老化酶重活化率的新化合物结构类型
Objective: To study the mechanisms of cholinesterase hydrolysis and organophosphate poisoning, aging and reactivation of cholinesterase, and to provide a theoretical basis for the molecular design of new reactivator. Methods: The semi-empirical quantum chemical method PM3 was used to study the interaction between acetylcholinesterase activity center and acetylcholine. Based on the prediction of the 3D spatial structure of acetylcholinesterase (AChE) in human brain, the docking technique was used to simulate acetylcholine , Four kinds of organic phosphate and acetylcholinesterase activity centers in three-dimensional structure of the molecular interactions. Results: Acetylcholine and cholinesterase activity center of tryptophan better docking, and the distance from the glutamic acid; 4 kinds of neurotoxic agents in the activity of cholinesterase center docking but different, and its Toxicity and the catalytic ternary inversely proportional to the distance, and proportional to the size of the role of static electricity. CONCLUSIONS: Cholinesterase catalyzes the possible formation of ternary from serine, histidine and tryptophan. Glutamic acid is indispensable in promoting proton transfer. A series of processes of aging and poisoning may result in the formation of aging enzyme May also be reactivated at the initial stage and predict the type of new compound structure that increases the initial rate of reactivation of the aged enzyme