Virtual screening of flavonoids as inhibitory agents of P-glycoprotein.

ABSTRACT

Flavonoids are constituents of fruits, vegetables, and plant derived beverages, as well as components in herbal dietary supplements. The objective of this investigation was to characterize and determine the effect of the Flavonoids on P-glycoprotein (P-gp) which is an important protein involved in multidrug resistance (MDR). Homology modeling of Pglycoprotein (Human) has been performed based on the crystal structure of the 2HYD (Chain A; Structure of a bacterial multidrug ABC transporter) by using Modeller software. With the aid of the molecular mechanics and molecular dynamics methods, the final model is obtained and is further assessed by procheck and verify 3D graph programs, which showed that the final refined model is reliable. With this model, a flexible docking study of P-glycoprotein with a group of Flavonoids which were selected from the previous publications was performed. The results indicated that GLN- 47, TYR -53, SER -83, ILE- 87, GLY -100, ARG -154 in P- glycoprotein are important determinant residues in binding as they have strong hydrogen bonding with Flavonoids. These hydrogen binding interactions play an important role for stability of the complex. Among the 13 Flavonoids docked, Acetylgenistin showed best docking result with Pglycoprotein. Our results may be helpful for further experimental investigations.