α-葡萄糖苷酶三维结构的同源模建及其对接研究

Homology Modeling of α-Glucosidase and Its Molecular Docking with Inhibitors

文章构建了α-葡萄糖苷酶的三维结构,并研究其与抑制剂分子的作用方式。以蜡状芽孢杆菌聚-1,6-葡萄糖苷酶的晶体结构为模板,利用同源模建法对α-葡萄糖苷酶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了修正和优化。在此基础上,使用InsightII软件包中的Biopolymer,Discover,Docking等模块,研究α-葡萄糖苷酶和其抑制剂伏格列波糖、米格列醇相互作用的结合位点和作用性质。模建出的α-葡萄糖苷酶三维结构,其可靠性经Ramachandran图和verify-3D图验证。α-葡萄糖苷酶与抑制剂主要通过氢键作用和疏水所用结合在一起。α-葡萄糖苷酶模型的建立和分子间作用的研究为α-葡萄糖苷酶抑制剂的虚拟筛选和对现有的抑制剂进行结构改造提供了一些有用的信息。

In this article, the homology model of the 3D structure of α-glucosidase was built and study the interaction between the enzyme and its inhibitor. The 3D structure of α-glucosidase was built by using the x-ray structure of oligo-1, 6-glucosidase from Bacillus cereus as a structural template. The most favorable structure was refined by molecular dynamics method. Then the Biopolymer, Discover and Docking modules in InsightII were used to investigated the possible binding site and inhibiting mechanism between α-glucosidase and its inhibitor voglibose, miglitol. The 3D structure was successfully built by homology method and its reliability was tested by PROCHECK and VERIFY-3D program. Voglibose and miglitol inhibit the catalytic action of α-glueosidase by binding in the active site through hydrogen bond and hydrophobic interactions. This research provided some useful information to virtual screen for potential α-glucosidase inhibitors and to modify the structure of present α-glucosidase inhibitor.