μ阿片受体三维结构模建与芬太尼类似物分子对接研究

The modeling of three-dimensional structure of humanμ-opioid receptor and the study of molecular docking of fentanyl analogs

本文通过牛视紫质蛋白质晶体结构使用Composer模建程序进行了人类μ阿片受体的同源模建,预测了μ阿片受体的二级结构,用Ramachandran图和ProTable验证模型的可靠性。得到的模型91%的氨基酸残基位于最佳区域,7个疏水区域表明有7个跨膜区与模型一致。并使用Surflex-Dock程序进行一系列芬太尼类似物分子与μ阿片受体的对接研究进而研究了其作用机制。活性位点主要包括ILE109,ASP112,TYR113,MET116,HIS262,TYR291。这些氨基酸残基都是芬太尼类似物与μ阿片受体的相互作用的主要残基。对接打分较高的分子均为与活性位点结合较好的分子,由此可对μ阿片受体有更深入的了解从而为设计出活性更高的芬太尼类化合物提供依据。

In this study, homologous modeling of human μ-opioid receptor was made on the basis of the crystal structure of bovine rhodopsin protein. The secondary structure of μ-opioid receptor was predicted, while the reliability of the model was tested and verified by Ramachandran plot and ProTab analysis. Then a series of researches of the molecules of fentanyl analogs docking to the/t-opioid receptor by using Surflex-Dock program were made, thus studying their interaction mechanism. Fully automatic flexible molecular docking （Surflex） was performed by using the possible active conformations of 70 fentanyl analogs and optimized 3D structure of p-opioid receptor. The active sites mainly consist of residues ILE 109, ASP 112, TYR113, MET116, HIS262 and TYR291. All these amino acid residues are all the main residues of interaction between fentanyl analogs and p-opioid receptor.