Structure Based Substrate Identification of Protein Kinase

Abstract

A protein kinase is a kinase enzyme that alter other molecules, most of them are proteins, by chemically adding phosphate groups to them (phosphorylation). The chemical activity of a kinase includes transferring a phosphate group from a nucleoside triphosphate (usually ATP) and covalently appending it to specific amino acids with a free hydroxyl group. Most kinases follow up on serine and threonine(serine/threonine kinases), others follow up on tyrosine (tyrosine kinases), and a number follow up on all of them (dual-specificity kinases). The substrate is perceived by kinase through the interactions of residues around the phosphorylation site in the substrate with the residues in the protein kinase. As we know that peptide is present on the surface of the substrate hence, we need to collect the x-ray structures of kinase-substrate peptide complexes. Through, these structures we will be able to identify the interaction between the peptide and the protein by visualising the structure. We will use these interactions to predict whether the unknown substrate will bind or not. To evaluate the potential of unknown peptide to be a substrate, you can model it in the active site and score the amino- amino interactions. Summing the interaction scores will give you the score of peptide. Peptides with a score above a threshold may be categorised as the substrates. (These scores have to be benchmarked against known substrates).