SERS and MD simulation studies of a kinase inhibitor demonstrate the emergence of a potential drug discovery tool.

ABSTRACT: We demonstrate the use of surface-enhanced Raman spectroscopy (SERS) as an excellent tool for identifying the binding site of small molecules on a therapeutically important protein. As an example, we show the specific binding of the common antihypertension drug felodipine to the oncogenic Aurora A kinase protein via hydrogen bonding interactions with Tyr-212 residue to specifically inhibit its activity. Based on SERS studies, molecular docking, molecular dynamics simulation, biochemical assays, and point mutation-based validation, we demonstrate the surface-binding mode of this molecule in two similar hydrophobic pockets in the Aurora A kinase. These binding pockets comprise the same unique hydrophobic patches that may aid in distinguishing human Aurora A versus human Aurora B kinase in vi

SUBMITTER: Karthigeyan D 

PROVIDER: S-EPMC4115535 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature