Exploring molecular flexibility and the interactions of Quercetin derivatives in the active site of α-glucosidase using molecular docking and charge density analysis

Molecular docking and charge density analysis were carried out to understand the geometry, charge density distribution and the electrostatic properties of Quercetin and its derivatives and for the same present in the active site of the alpha-glucosidase of S. cerevisiae. By using molecular docking, the binding energies and nearest amino acids were calculated. Due to absence of the bioactive conformation from experimental data, conformations were elected in this text from the docking procedure based on chemometric techniques in order to represent the set of the promising configurations. The optimized geometries of these molecules were performed using Hartree-Fork and Density Functional Theory (DFT-B3LYP) combined with the theory of atoms in molecules (AIM). It is observed that the geometrical, bond topological and the electrostatic properties of the molecules are significantly altered in the active site. The introduced substituent groups with different volume and polarity have some influence on the variations of charge and polarization when the molecules present in the active site. All of the dipole moments of the three molecules are changed in the active site on compared with the gas phase, especially the one introduced large polar substituent group. Comparing with the parent Quercetin molecule, the two derivatives have lower energy gaps between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) in the active site, which illustrates their lower stability and higher inhibition activity. The comparative study on the geometrical and electrostatic properties of these synthetic or natural molecules is useful for further designing new drugs for the better treatment of diabetes disease. (C) 2016 Elsevier B.V. All rights reserved.