乙酰胆碱酯酶抑制剂虚拟筛选方法研究

在虚拟筛选过程中，虚拟筛选策略和方法是获取结果的基础，但需要通过实验数据来检验。获得虚拟筛选合理的限制因素，将为大规模虚拟筛选提供方法依据。通过建立乙酰胆碱酯酶抑制剂的活性检测方法，检测了4000多个化合物的生物活性，并发现了34个活性较高的化合物，同时将设计的6个不同的虚拟筛选方法分别用于2个乙酰胆碱醋酶抑制剂虚拟筛选模型。将所预测的可能活性化合物及两模型共有的可能活性化合物分别与实验所得的活性化合物对照，综合分析讨论虚拟筛选乙酰胆碱酯酶抑制剂的重要因素和进一步富集活性化合物的方法，为大规模的虚拟筛选乙酰胆碱醋酶抑制剂提供可靠依据，并为其他基于蛋白酶结构的虚拟筛选提供参考。

Method research on virtual screening of acetylcholinesterase inhibitors

In the process of virtual screening, various results of virtual screening base on various virtual screening strategies and methods. The rational methods must be got by experiment, it can instruct large scale virtual screening. The assay method of acetylcholinest-erase( AChE) inhibitors was introduced in this paper. More than four thousand compounds were detected by this method, and 34 compounds with higher bioactivities were found. Based on two complex crystal structures, two virtual screening model were established to forecast the possible activity compounds from the compounds detected by applying 6 different methods. The two set possible activity compounds of the two model and the common possible activity compounds were compared with the activity compounds obtained from bio-assay. The important factors of virtual screening acetylcholinesterase (AChE) inhibitors and the methods to enrich activity compounds were analyzed and discussed. Some advices for large scale virtual screening of acetylcholinesterase( AChE) inhibitors were put forward.