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Title: An in silico approach for the discovery of CDK5/p25 interaction inhibitors
Authors: Zhang, B. 
Corbel, C.
Guéritte, F.
Couturier, C.
Bach, S.
Tan, V.B.C.
Keywords: CDK5
Molecular dynamics
Protein-protein interaction inhibitor
Virtual screening
Virtural alanine scanning
Issue Date: Jul-2011
Citation: Zhang, B., Corbel, C., Guéritte, F., Couturier, C., Bach, S., Tan, V.B.C. (2011-07). An in silico approach for the discovery of CDK5/p25 interaction inhibitors. Biotechnology Journal 6 (7) : 871-881. ScholarBank@NUS Repository.
Abstract: The lack of selectivity of all existing ATP competitive inhibitors for a single cyclin-dependent kinase (CDK) has led us to redirect the structure-based molecule design from targeting the classic ATP-binding pocket in CDK5 toward the CDK5/p25 interface. The aim was to seek novel inhibition mechanisms to interrupt protein-protein interactions. A combined strategy of alanine-scanning calculations for locating binding sites, virtual screening for small molecules, molecular dynamics simulations for examining the binding stability of virtual screening hits and bio-assays for testing the level of inhibition was set up and used to explore novel inhibitors capable of interrupting the interactions between the proteins, and consequently of inhibiting the kinase activity. Two compounds were shown to inhibit the complex formation between CDK5 and p25 through p25 binding. They could open avenues for the discovery of new types of structures that prevent interactions between CDK5 and p25 or other CDK and activator proteins, and, more importantly, provide leads in the development of selective inhibitors among CDKs. Accompanying article Corbel et al. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Source Title: Biotechnology Journal
ISSN: 18606768
DOI: 10.1002/biot.201100139
Appears in Collections:Staff Publications

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