A comparative analysis of binding sites between human PKD1 and PKC1 based on homology modelling,molecular dynamics simulation and docking studies

Human protein kinase C1 (PKC1) and protein kinase D1 (PKD1) are two closely related enzymes, which have emerged as key regulators of many important cellular processes. In this study, 3D models of human PKC1 and PKD1 were constructed based on homology modelling and molecular dynamics simulations. A novel 2,6-naphthyridine is a potent and selective inhibitor for human PKD1 and not for PKC1, which was docked into them and positioned in their active sites with different orientations. By comparison of active site architectures between human PKC1 and PKD1, the possible reasons affecting their inhibitor binding were proposed. In addition, some residues are identified as critical residues for inhibitor binding.