Docking and 3D-QSAR modeling of cyclin-dependent kinase 5/p25 inhibitors

Zaheer Ul Haq, Reaz Uddin, Kok Wai Lam, Abdul Wadood, Nordin Haji Lajis

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Structure-based 3D-QSAR approaches (CoMFA and CoMSIA) were applied to understand the structural requirements of the Cyclin-dependent kinase 5/p25 inhibitors. Cyclin-dependent kinase 5 (CDK5) is believed to play an important role in the development of the central nervous system during the process of mammalian embryogenesis. Genetic algorithm based docking program (GOLD) was successfully utilized to orient the compounds inside the binding pocket of the CDK5/p25 structure. The adapted alignment method with the suitable parameters resulted in a reliable model. Furthermore, the final model was robust enough to forecast the activities of test compounds, satisfactorily. The contour maps were produced around the functional groups to understand the SAR requirements. Moreover, we also investigate the structural attributes of the inhibitors which make them selective toward CDK5/p25 over its close counterpart, i.e., CDK2. The study could be helpful to rationalize the new compounds with better inhibition and selectivity profiles against CDK5/p25.

Original languageEnglish
Pages (from-to)1149-1161
Number of pages13
JournalJournal of Molecular Modeling
Volume17
Issue number5
DOIs
Publication statusPublished - May 2011
Externally publishedYes

Fingerprint

Cyclin-Dependent Kinase 5
inhibitors
requirements
central nervous system
genetic algorithms
forecasting
selectivity
alignment
profiles
Neurology
Functional groups
Genetic algorithms
Cyclin-Dependent Kinases

Keywords

  • 3D-QSAR
  • CDK5/p25
  • CoMFA
  • CoMSIA
  • Docking

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Catalysis
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Docking and 3D-QSAR modeling of cyclin-dependent kinase 5/p25 inhibitors. / Ul Haq, Zaheer; Uddin, Reaz; Lam, Kok Wai; Wadood, Abdul; Lajis, Nordin Haji.

In: Journal of Molecular Modeling, Vol. 17, No. 5, 05.2011, p. 1149-1161.

Research output: Contribution to journalArticle

Ul Haq, Zaheer ; Uddin, Reaz ; Lam, Kok Wai ; Wadood, Abdul ; Lajis, Nordin Haji. / Docking and 3D-QSAR modeling of cyclin-dependent kinase 5/p25 inhibitors. In: Journal of Molecular Modeling. 2011 ; Vol. 17, No. 5. pp. 1149-1161.
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