Virtual screening of flavonoids as inhibitory agents of P-glycoprotein.
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Date
2011-07
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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.
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Keywords
Acetylgenistin, Flavonoids, Homology modeling, P-glycoprotein (P-gp), Molecular dynamics
Citation
Kumar N Udaya, Sailendra M, Peddanna K, Prasad E Maruthi, Deepika G, Seshapani P, Latha L Shobhaswarna, Rayalu D Jayasimha. Virtual screening of flavonoids as inhibitory agents of P-glycoprotein. International Journal of Applied Biology and Pharmaceutical Technology. 2011 Jul-Sept; 2(3): 130-140.