Designing of Protein Kinase C β-II Inhibitors against Diabetic complications: Structure Based Drug Design, Induced Fit docking and analysis of active site conformational changes



Balakrishnan Vijayakumar1 & Devadasan Velmurugan1, 2*



1Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Maraimalai (Guindy) campus, Chennai 600 025, INDIA; 2Bioinformatics Infrastructure Facility (BIF), University of Madras, Maraimalai (Guindy) campus, Chennai 600 025, INDIA


Email; *Corresponding author


Article Type




Received June 09, 2012; Accepted June 16, 2012; Published June 28, 2012



Protein Kinase C β-II (PKC β-II) is an important enzyme in the development of diabetic complications like cardiomyopathy, retinopathy, neuropathy, nephropathy and angiopathy. PKC β-II is activated in vascular tissues during diabetic vascular abnormalities. Thus, PKC β-II is considered as a potent drug target and the crystal structure of the kinase domain of PKC β-II (PDB id: 2I0E) was used to design inhibitors using Structure-Based Drug Design (SBDD) approach. Sixty inhibitors structurally similar to Staurosporine were retrieved from PubChem Compound database and High Throughput Virtual screening (HTVs) was carried out with PKC β-II. Based on the HTVs results and the nature of active site residues of PKC β-II, Staurosporine inhibitors were designed using SBDD. Induced Fit Docking (IFD) studies were carried out between kinase domain of PKC β-II and the designed inhibitors. These IFD complexes showed favorable docking score, glide energy, glide emodel and hydrogen bond and hydrophobic interactions with the active site of PKC β-II. Binding free energy was calculated for IFD complexes using Prime MM-GBSA method. The conformational changes induced by the inhibitor at the active site of PKC β-II were observed for the back bone Cα atoms and side-chain chi angles. PASS prediction tool was used to analyze the biological activities for the designed inhibitors. The various physicochemical properties were calculated for the compounds. One of the designed inhibitors successively satisfied all the in silico parameters among the others and seems to be a potent inhibitor against PKC β-II.



PKC β-II, HTVs, SBDD, IFD, Prime MM-GBSA, Chi angles, ADME/Tox



Vijayakumar & Velmurugan, Bioinformation 8(12): 568-573 (2012)

Edited by

P Kangueane






Biomedical Informatics



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