Molecular Docking Estimation of Some Dibenzalacetone Derivatives Interaction with G Protein Receptor Kinase (GRK)

This work employs DFT and molecular docking calculations to investigate the mechanism of interaction between G protein receptor kinases (GRKs) and dibenzalacetone derivatives (DBADs). GRKs are necessary for various physiological functions and are implicated in several diseases, including heart failure and cancer, making them critical therapeutic targets. Numerous DBADs, with various substitutes, were selected in this study for their diverse bioactive application. This in vitro study was conducted to determine the inhibition mechanism of DBADs and to explore additional factors in the structure-activity relationship. DFT calculations were performed to optimize the chemical structures of DBADs at the B3LYP level of theory, using the 6-311G(d,p) basis set. Molecular docking was subsequently performed to extract interaction details, including ionic H-bonds and other interaction modes within the active site of GRK (PDB ID: 3NYO). The findings show that the interaction between GRK and the target DBADs occurs within the same cavity of GRK- adenosine monophosphate AMP, the typical substrate, with a higher inhibition constant ranging from 0.2 to 1.9 kcal/mole, higher than AMP, but involves different amino acids than AMP. These results suggest that the target DBADs can act as bioactive compounds and function as competitive inhibitors, opening the way for further pharmaceutical examinations.