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Qi Y.J.,Northwest University for Nationalities | Zhao Y.M.,Northwest University for Nationalities | Lu H.N.,Northwest University for Nationalities | Wang X.E.,Northwest University for Nationalities | Jin N.Z.,Gansu Province Computing Center
Computational and Theoretical Chemistry | Year: 2016

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 α-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. © 2016 Elsevier B.V.

Qi Y.,Northwest University for Nationalities | Zhao Y.,Northwest University for Nationalities | Wang X.,Northwest University for Nationalities | Lu H.,Northwest University for Nationalities | Jin N.,Gansu Province Computing Center
Journal of Theoretical and Computational Chemistry | Year: 2016

Molecular docking and charge density analysis were carried out to understand the geometry, charge density distribution and electrostatic properties of one of newly synthesized 4-substituted-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates (PDE), which is regarded as the best α-Glucosidase inhibitor among the hydropyridine dicarboxylate derivatives. The different bonding models of the PDE molecule in the active sites of proteins Human serum albumin (HSA) and Saccharomyces cerevisiae α-glucosidase (SAG) are firstly compared, which is important to understand the different intermolecular interactions between drug-transport protein and drug-target protein. The deformation density maps suggest that the electron densities of the PDE molecule are redistributed when it presents in the active sites. When the molecule presents in the active site of the SAG, it is evident to find that the negative region does not appear at the vicinity of the oxygen atoms on one of the carboxylic acid dimethyl ester group. Frontier molecular orbital density distributions for the PDE molecule are similar in all forms. The highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) energy gaps in the active sites are higher than that of the molecule in pure solution phase. It is generally noticed that all of the orientations of the dipole moment vectors are reoriented in both active sites. These fine details at electronic level allow to better understand the exact drug-transport protein and drug-target protein interactions. © 2016 World Scientific Publishing Company.

PubMed | Gansu Province Computing Center and Northwest University for Nationalities
Type: | Journal: Computational biology and chemistry | Year: 2017

As one of the most investigated flavonoids, apigenin, is considered to be a strong -glucosidase inhibitor. However, the clinical utility of apigenin is limited due to its low solubility. It was reported that the solubility and biological activity can be improved by introducing sole carboxyalkyl group into apigenin, especially the 7-substitution. With the increase of length of the alkyl chain in carboxyalkyl group, B ring of the apigenin derivative is embedded much more deeply into the binding cavity while the carboxyalkyl stretches to the neighboring cavity. All of the terminal carboxyl groups form hydrogen bonding interactions easily with the surrounding polar amino acids, such as His239, Ser244, Arg312 and Asp349. Thus, the electron density values of the carbonyl in the carboxyl group become higher than the solution status due to the strong molecular interactions. In fact, electron densities of most of the chemical bonds are decreased after molecular docking procedure. On compared with the solution phase, however, dipole moments of most of these molecules are increased, and their vectors are reoriented distinctly in the active sites. It is noticed that all of the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) are distributed throughout the whole parent apigenin ring in solution phase, whereas the disappeared situation happened on the B rings of some molecules (II-IV) in the active site, leading to higher energy gaps.

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