Role of Hydrogen Bonding and Hydrophobic Interactions on the Stabilization of Myoglobin (Globular Protein)-Primaquine-4-Dicyanomethylene-2,6-Dimethyl-4H-pyran (DDP) Conformers

Abstract

Molecular docking (MD) approach on the binding interaction of two competing ligands with a well-known globular protein, myoglobin (MB) was carried out. Docking studies of 4-dicyanomethylene- 2,6-dimethyl-4H-pyran (DDP) dye and an anti-malarial drug, primaquine (PRQ) were considered as the guest molecules in the presence of myoglobin as the host molecule. Docking studies of dye-myoglobin conformers reveals that the dye resides predominantly in between the helices C and D, which are stabilized and governed by hydrogen-bonding interactions. Further, the dye is also stabilized through hydrophobic interactions when confined to E and F helices of the protein. However, the drug prefers to reside in all the domains of the polypeptide chain structure of myoglobin resulting in a larger stability when compared to that of dye-protein complex. Interestingly, the displacement of dye from the binding sites of myoglobin was found to be ineffective in the presence of drug. On the contrary, the dye efficiently displaces the drug entirely to a single confined region (between C and D, E and between F and G) of the protein molecule. Docking studies signifies that the hydrogen bonding donor and acceptor sites were involved in the stabilization of complex thereby provides a clear elucidation on the binding nature of two competing guest molecules in the presence of host molecule. Molecular docking technique was used as an efficient and reliable tool to determine the various bimolecular interactions existing between protein-dye and protein- drug complexes.