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Binding of BIS like and other ligands with the GSK-3 beta kinase: a combined docking and MM-PBSA study

Jena, Nihar R (2012) Binding of BIS like and other ligands with the GSK-3 beta kinase: a combined docking and MM-PBSA study. In: Journal of Molecular Modeling, 18 (2). pp. 631-644.

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Binding of several bisindolylmaleimide (BIS) like (BIS-3, BIS-8 and UCN1) and other ligands (H89, SB203580 and Y27632) with the glycogen synthase kinase-3 (GSK-3 beta) has been studied using combined docking, molecular dynamics and Poisson-Boltzmann surface area analysis approaches. The study generated novel binding modes of these ligands that can rationalize why some ligands inhibit GSK-3 beta while others do not. The relative binding free energies associated with these binding modes are in agreement with the corresponding measured specificities. This study further provides useful insight regarding possible existence of multiple conformations of some ligands like H89 and BIS-8. It is also found that binding modes of BIS-3, BIS-8 and UCN1 with GSK-3 beta and PDK1 kinases are similar. These new insights are expected to be useful for future rational design of novel, more potent GSK-3 beta-specific inhibitors as promising therapeutics.

Item Type: Journal Article
Publication: Journal of Molecular Modeling
Publisher: Springer
Additional Information: Copyright of this article belongs to Springer.
Keywords: BIS like inhibitors;Docking;Glycogen synthase kinase-3 beta (GSK-3 beta);MM-PBSA;Protein-drug binding
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 27 Feb 2012 10:56
Last Modified: 27 Feb 2012 10:56
URI: http://eprints.iisc.ac.in/id/eprint/43669

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