IDENTIFICATION OF HUMAN cAMP DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT INHIBITORSAbstract
Cyclic adenosine monophosphate (cAMP) dependent protein kinase plays a major role in cell signaling pathway. Over expression of extracellular cAMP dependent protein kinase catalytic subunit caused tumorgenesis in prostate. This protein may provide a base for the design of clinically applicable therapeutic strategies. In order to develop potential inhibitor of cAMP dependent protein kinase catalytic subunit, a high throughput virtual screening of zinc natural compounds database was conducted. Furthermore, QikProp, ADMET predictor and MM-GBSA was performed for ADME (Absorption, Distribution, Metabolism and Elimination), toxicity and binding energy prediction for ligands, respectively. Finally, molecular dynamics simulation was performed to get potential inhibitor. The crystal structure of cAMP dependent protein kinase was used for current study. The entire library of natural compounds was screened using HTVS for the primary level of screening. The binding of the compounds was studied using standard precision followed by Extra Precision algorithm of Glide Docking. On the basis of docking scores top ten hit compounds were selected for further analysis. The Binding affinity was further calculated using MMGBSA. The interaction studies using molecular docking and MMGBSA revealed significant docking scores and dG bind. Molecular dynamic simulation studies of zinc0B511410-protein complex for 50 ns shows the stability of system. Further experimental evaluation of the lead compounds can prove their potential as a therapeutic inhibitor.
U. Khanam, B. K. Malik and B. Rathi*
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University Noida, Uttar Pradesh, India
06 January, 2017
15 March, 2017
22 March, 2017
01 August, 2017