Molecular Docking Studies on Binding Sites, Interactions and Stability of Globular Protein, Ovalbumin (OVA) with 4-Dicyanomethylene-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCDAP) Dye in presence of various Flavonoids of Psidium guajava

Abstract

Introduction: Molecular docking (Mol.Doc) techniques were employed to ascertain the binding sites, interactions and stability of a globular protein with an Intramolecular Charge Transfer dye in the presence of flavonoids extracted from guava fruit leaves. Ovalbumin (OVA) as the host, 4-dicyanomethylene-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCDAP) dye as the guest and the flavonoids as competing guest molecules are employed in the study.

Objectives: OVA as the host, DCDAP dye as the guest and the flavonoids as competing guest molecules are employed in the study to establish the bimolecular forces governing the stability of the host-guest complex in the presence of a competing guest molecule.

Methods: Mol.Doc studies were carried out using Autodock software version 4.2 as performed in the studies regarding dye-protein-drug system. In docking studies, Lamarckian genetic algorithm

is applied. As the result of several conformers generated, the best 10 stable clusters were selected in the descending order of binding energy (B.E) conformation ranking. The 10 conformations were selected and further saved in pdb format. OVA-DCDAP complex was, further docked with a set of 16 flavonoids based on subject to Lipinski rule of Five.

Results: The host-guest conformers were categorized based on the docking score correlated to binding energy and the stability of the complex are governed by the bimolecular interactions. Studies reveal that protein-dye complex is relatively less stable than protein-dye-flavonoid complex. The stability is attributed to several conventional hydrogen-bonding interactions existing between dye-flavonoid and the amino acid residues of OVA, act as the hydrogen-bonding donor while dye acts as hydrogen-bonding acceptor. Molecular docking of flavonoid binding to protein-dye complex results in an enhanced stability of the complex.  Further, there exists no direct binding of dye with flavonoid when docked simultaneously. Moreover, flavonoid and dye reside far apart from each other in distinct sites of OVA.

Conclusions: The stability upon complex formation is correlated to the docking of the guest molecule in the binding domains of OVA. The presence of multiple hydrophobic interactions such as pi-pi, pi-alkyl, pi-cation or anion, pi-sigma and pi-amide along with conventional hydrogen-bonding and weak van der Waals in OVA-dye -flavonoid complex does not destabilize, instead promote the binding stability.