Acta Phys. -Chim. Sin. ›› 2014, Vol. 30 ›› Issue (2): 371-381.doi: 10.3866/PKU.WHXB201312192

• BIOPHYSICAL CHEMISTRY • Previous Articles     Next Articles

Homology Modeling, Molecular Docking, and 3D-QSAR of Indirubin Analogues as CDK1 Inhibitors

ZHANG Qing-Qing1, YAO Qi-Zheng1, ZHANG Sheng-Ping1, BI Le-Ming1, ZHOU Zhi-Guang1, ZHANG Ji2   

  1. 1 School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P. R. China;
    2 Department of Physical Chemistry, China Pharmaceutical University, Nanjing 210009, P. R. China
  • Received:2013-10-29 Revised:2013-12-19 Published:2014-01-23
  • Contact: YAO Qi-Zheng, ZHANG Ji;
  • Supported by:

    The project was supported by the National Key Subject of Drug Innovation, China (2009ZX09103-149).


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 cell cycle target for cancer drug discovery. In this paper, we use the cell division control protein 2 homolog as a template to homologically 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-QSARmodels, and shows the best calculated results (CoMFA: q2=0.681, r2=0.909, and rpred.2=0.836; DS: q2= 0.579, r2=0.971, and rpred.2=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.

Key words: Cyclin-dependent kinase 1, Indirubin, 3D-QSAR, CoMFA, Homology modeling


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