咪唑烷二酮类PTP1B抑制剂的分子对接研究  

Molecular docking studies on imidazolidinedione based PTP1B inhibitors

作　　者：平川[1] 王润玲[1] 刘梦源[1] 徐为人[2] 周慧[1] 

机构地区：[1]天津医科大学药学院药物化学教研室,天津300070 [2]天津药物研究院

出　　处：《天津医科大学学报》2008年第4期448-451,共4页Journal of Tianjin Medical University

摘　　要：目的:设计蛋白酪氨酸磷酸酯酶1B(PTP1B)抑制剂。方法:利用ChemOffice 2008绘制出70个具有咪唑烷二酮结构母核的小分子化合物平面结构,然后利用Schrodinger Suite 2007构建小分子化合物库、蛋白结构优化、分子对接。结果:分子对接研究表明,设计的小分子化合物大部分对接得分优于原始配体,都可与活性位点底部和顶部的残基形成氢键,而原始配体只能与活性位点顶部的残基形成氢键。结论:设计小分子与PTP1B的结合能力理论上优于原始配体。Objective： To develop protein tyrosine phosphatase 1B （PTP1B） inhibitors. Methods： Seventy small imidazolidinedione scaffold-based molecules were drawn using software ChemOffice 2008. Then, the small molecular library, protein structure optimization and molecular docking were carried out using software Schrodinger Suite 2007. Results： The docking study suggested that the most of the designed molecules＇ Docking scores were higher than the original ligand in PTP1B. These molecules could form hydrogen bonds with the residues in the bottom of the active site and the top of the active site. But the original complex could only exhibit hydrogen bonds with the top of the active site. Conclusion： The binding affinity of the designed molecules is theoretically higher than the original ligand in PTP1B.

关 键 词：蛋白酪氨酸磷酸酯酶1B 咪唑烷二酮 糖尿病 计算机辅助药物设计 分子对接 胰岛素抵抗 

分 类 号：R914.2[医药卫生—药物化学]