Molecular docking studies on the binding interaction and stability of ovalbumin with an intramolecular charge transfer dye 4-dicyanomethylene-2,6-dimethyl-4H-pyran in the presence of an antibiotic: Tetracycline

Abstract

Molecular docking (MD) studies of an Intramolecular Charge Transfer (ICT) dye, 4-Dicyanomethylene2,6-Dimethyl-4-Hpyran (DDP) dye with a globular protein, ovalbumin (OVA) were carried out in the presence of antibiotic drug, tetracycline (TTC). OVA is classified as a globular protein and the binding stability of OVA-DDP versus OVA-TTC was ascertained from energetics (docking of protein-dye/drug) and molecular interaction parameters existing between the host and guest molecule. OVA is the host molecule and the drug and dye are the guest molecule under considerations. MD studies reveals the location of DDP dye in five distinguishably different active binding sites of OVA corresponding to various sub domains and the binding energy of dye differs significantly based on the conformers generated. Similarly, the drug is bound to several sub domains of OVA such the co-existence of eight different unique conformers is visualized among which TTC is bound to four active sites. Docking studies reveals TTC-OVA complex is relatively less stable than DDP-OVA complex even though the stability is attributed to several conventional hydrogen-bonding (HB) interactions existing between TTC and amino acid (AA) residues of OVA. TTC predominantly acts as a HB acceptor and the AA residues as the donor. The extent of HB interactions predominates over hydrophobic interactions in TTC-OVA compared to DDP-OVA complex. Interestingly, docking of TTC to DDP-OVA complex results in an enhanced stability of the dye-protein complex. Interestingly, there exist no direct binding of dye with drug when docked simultaneously. Both dye and drug reside far apart from each other in conformationally distinct active sites of OVA is authenticated. MD studies further, elucidates that DDP dye is bound to several AA residues through conventional and non-conventional HB interactions accompanied with hydrophobic interactions, π -π, π -alkyl interactions and weak van der Waals forces such that the presence of drug does not destabilize the complex, rather promote more binding interactions. MD is used as an efficient tool and non-evasive technique in establishing the stability of two distinct guest molecules competing with same host molecule (protein) is imparted in the present study.