CCK1受体的同源模拟和分子对接研究

Homology Modeling and Molecular Docking on CCK_1 Receptor

采用同源建模法对CCK1受体的三维结构进行了模拟,并采用分子动力学方法对模型进行修正和优化,再采用与训练集激动剂和拮抗剂分子对接的方法分别得到激动状态和拮抗状态CCK1受体的三维结构模型.得到的模型使用DOCK对接软件对训练集中的分子进行对接,所得结果与其实际活性拟合度较好,说明我们建立的激动和拮抗状态下的CCK1受体的三维结构模型比较合理,可以作为化合物虚拟筛选的模型对新化合物进行虚拟筛选.

The three-dimensional structure models of a CCKI receptor was built by a homology method, and then refined using a molecular dynamics method. The optimazation of the models into ＂agonist-bound＂ and ＂antagonist-bound＂ ones was performed using a training set of compounds docked for CCK1 receptor models, respectively. Agonist in test set was docked into an ＂agonist-bound＂ model and antagonist in test set was docked into an ＂antagonist-bound＂ model using DOCK program. There was a good linear relationship between dock scores and the experimental affinities. Such work highlighted the rational structures for the ＂agonist-bound＂ and ＂antagonist-bound＂ CCK1 receptor models, which can be used for vitual screening to discover more potent compounds.