Drug Designing: Open Access
Open Access
ISSN: 2169-0138
ISSN: 2169-0138
Baljinder K.Grewal and M.E.Sobhia
Accepted Abstracts: Drug Design
PKCβII is emerging as an important therapeutic target due to its significant participation in various diabetic complications. Two crystal structures of PKCβII and few selective PKCβII inhibitors are reported. Detail structural insight of interaction of clinically important molecule is of prime importance for rational designing of new inhibitors. The water molecule present in ligands vicinity can greatly affects the protein-ligand interactions, in PKCβII six water molecules are present near ligand binding site within the range of 5 Å. Molecular dynamics (MD) study using MM-PB(GB)SA approach is combined with molecular docking to elucidate the binding mode analysis of selective PKCβII inhibitors ruboxistaurin, enzastaurin; and the role of crystal water in protein-ligand interactions. The results were compared with the co-crystallized PKCβII- 2-methyl-1H-indol-3-yl-BIM- 1(2mBIM) complex. Binding free energies, decomposition energy per residue, hydrogen bond of PKCβII complexes were also studied and compared with experimental findings. Binding free energies shows the presence of two crystal water being favorable for ligand-protein interactions, Hydrogen bond analysis showed the stability of two hydrogen bonds in all ligands. In addition, the present study highlighted another important interactions, interacting residues and type of interactions which will accelerate the drug designing and development processes of PKCβII inhibition.
Baljinder K.Grewal is pursuing her Ph.D in Pharmacoinformatics from National Institute of Pharmaceutical Education and Research, India. She will be completing her degree by March 2013. She published two research articles and one review article in international journals. Her thesis work in on molecular modeling study on protein kinase inhibitors where different computer aided tools viz. QSAR, Pharmacophore-mapping, molecular dynamics study, Quantum chemical studies are employed to rationaaly design the selective protein kinase inhibitors.