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Medicinal Chemistry Research

, Volume 23, Issue 6, pp 3092–3095 | Cite as

A comparative molecular dynamics simulation study to assess the exclusion ability of novel GSK3β inhibitors

  • Pradeep Hanumanthappa
  • Rajanikant G. KrishnamurthyEmail author
Original Research

Abstract

The involvement of glycogen synthase kinase 3β (GSK3β) in eukaryotic cell apoptosis and the extensive potency of GSK3β inhibitors to block cell death has made it a potential drug discovery target for many grievous human disorders. GSK3β is phylogenetically related to the CDKs, such as CDK1 and CDK2, which are suggested to be the off-target proteins of GSK3β inhibitors. The present work is focused on delineating the interaction profiles crucial for the exclusion ability of GSK3β inhibitors against CDKs. With this objective in mind, we carried out molecular dynamic simulation studies on previously identified GSK3β inhibitors, docked to the kinase-binding domains of GSK3β, CDK1 and CDK2. The binding mode analysis of these ligands showed all the essential binding interactions required for the selective inhibition of GSK3β. Further, the crucial protein–ligand interactions and GSK3β-selective mechanisms of identified ligands were analyzed and discussed.

Keywords

GSK3β CDK1 CDK2 Target specificity Molecular dynamics simulation 

Notes

Conflict of interest

None.

Supplementary material

Supplementary material 1 (MPG 8080 kb)

Supplementary material 2 (MPG 19470 kb)

Supplementary material 3 (MPG 19210 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Pradeep Hanumanthappa
    • 1
  • Rajanikant G. Krishnamurthy
    • 1
    Email author
  1. 1.School of Biotechnology Centre for BioinformaticsNational Institute of Technology CalicutCalicutIndia

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