物理化学学报Issue(2)：371-381,11.DOI:10.3866/PKU.WHXB201312192
靛玉红类CDK1抑制剂的同源模建、分子对接及3D-QSAR研究
Homology Modeling, Molecular Docking, and 3D-QSAR of Indirubin Analogues as CDK1 Inhibitors
摘要
Abstract
The abnormal expression of cyclin-dependent kinase 1 (CDK1) leads to stagnation of the G2 phase and a variety of tumors. Therefore, CDK1 has been reported recently as an ideal cellcycle target for cancer drug discovery. In this paper, we use the celldivision control protein 2 homolog as a template to homological y model the protein of CDK1 that is subsequently docked with the inhibitors of indirubin analogues. Three molecular alignment methods were used, and the corresponding three-dimensional quantitative structure-activity relationship (3D-QSAR) models were built using the comparative molecular field analysis (CoMFA) protocol in Sybyl 7.1 and the 3D-QSAR protocol (abbreviated for DS) in Discovery Studio 3.0. It was found that the molecular alignment method combining molecular docking with public template is most suitable for building the 3D-QSAR models, and shows the best calculated results (CoMFA:q2=0.681, r2=0.909, and r2pred.=0.836;DS:q2=0.579, r2=0.971, and r2pred.=0.795, where q2 denotes the cross-validated correlation coefficient and r2 denotes the non-cross-validated correlation coefficient). This paper may provide significant theoretical foundation for designing novel CDK1 inhibitors by carrying out structural modifications of indirubin analogues.关键词
细胞周期蛋白依赖性激酶1/靛玉红/3D-QSAR/比较分子场分析/同源模建Key words
Cyclin-dependent kinase 1/Indirubin/3D-QSAR/CoMFA/Homology modeling分类
化学化工引用本文复制引用
张青青,姚其正,张生平,毕乐明,周之光,张骥..靛玉红类CDK1抑制剂的同源模建、分子对接及3D-QSAR研究[J].物理化学学报,2014,(2):371-381,11.基金项目
The project was supported by the National Key Subject of Drug Innovation, China (2009ZX09103-149)@@@@国家“重大新药创制”科技重大专项(2009ZX09103-149)资助 （2009ZX09103-149）
