A Structure Based Approach To Search Potential Inhibitors Of Human Calcium-calmodulin Dependent Protein Kinase IV | 39048
Journal of Biotechnology & Biomaterials
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Calcium-calmodulin dependent protein kinase IV (CAMK4) is a key player of calcium-dependent gene expression and
thus involved in varieties of cellular function including cell signaling and neuronal survival and associated with many
diseases including cancer. Here, we first studied the interaction of curcumin with human CAMK4 at physiological pH 7.2
by using molecular docking, molecular dynamics (MD) simulation and fluorescence & surface Plasmon resonance methods.
After docking of curcumin to the CAMK4 active site we performed MD simulations for both keto and enol forms of curcumin-
CAMK4 complexes for a reasonably long time (150 ns) to see the overall stability of the ligand-protein complex. We found
that a significant conformational change occurred in the CAMK4 upon binding of curcumin. The experimental results show
that the fluorescence intensity of CAMK4 was significantly increased while addition of curcumin. We have further measured
the binding affinity of curcumin to the CAMK4 using SPR and found kD=3.7×10-8 M. Based on such study, we have designed
several pyrimidine and thiol based compounds which were successfully synthesized. Several of these ligands are showing
their binding affinity in the nm range with the CAMK4. This study will provide insights into designing of the new inspired
coumarin derivatives as therapeutic agents against many life threatening diseases. Finally, we have successfully designed and
synthesized very effective small molecule Cam kinase inhibitors, serves as a model for the development of novel phamacophore
for therapeutic intervention.
Md Imtaiyaz Hassan has completed his PhD from All India Institute of Medical Sciences and Postdoctoral studies from Saint Louis University School of Medicine, USA. He is working as an Assistant Professor in a Premier Central University, Jamia Millia Islamia, New Delhi. He has published more than 70 papers in reputed journals and has been serving as an Editorial Board Member of Journal of Protein and Proteomics, Journal of Natural Science, Biology and Medicine and many other journals.