多巴胺D2受体三维结构预测及与激动剂配体相互作用的研究

STUDY ON THE 3DSTRUCTURE PREDICTION OF DOPAMINE D2RECEPTOR AND ITS INTERACTION WITH AGONISTS

以细菌视紫红质（ｂａｃｔｅｒｉｏｒｈｏｄｏｐｓｉｎ）的三维晶体结构为模板，预测了多巴胺Ｄ２受体跨膜区的７个α螺旋肽段的三维结构。根据定点突变实验数据以及预测的受体三维结构，确定了激动剂配体结合腔由Ａｓｐ８６，Ｓｅｒ１４１，Ｓｅｒ１４４等１２个氨基酸残基组成。为了校正和检验所得的模型，分别以一组刚性、一组柔性的激动剂与受体对接（ＤＯＣＫ），分析－ｌｏｇＩＣ５０和结合能Ｅｂ相关性，较好的结果说明该模型是可靠的。

A model of dopamine D2 receptor transmembrane helices was constructed using the bacteriorhodopsin Xray coordinates as a template. Based on the information from sitedirected mutagenesis, the binding pocket, including nine amino acid residues besides indispensable Asp 86, Ser 141 and Ser 144 residues, was defined. In order to rectify the 3Dstructure of dopamine D2 receptor and test the binding sites of the receptor agonists, two sets of dopamine D2 receptor agonists (one is rigid, the other is flexible) were selected for docking. A result of good correlation betweenlogIC50 and binding energy Eb indicated that the predicted model is reliable for the investigation of the receptorligand interaction and design of new active molecules.