Gansu Province Computing Center

Lanzhou, China

Gansu Province Computing Center

Lanzhou, China
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Qi Y.J.,Northwest University for Nationalities | Lu H.N.,Northwest University for Nationalities | Liang J.X.,Northwest University for Nationalities | Zhao Y.M.,Northwest University for Nationalities | And 2 more authors.
Computational Biology and Chemistry | Year: 2017

As one of the most investigated flavonoids, apigenin, is considered to be a strong α-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. © 2017 Elsevier Ltd


Qi Y.J.,Northwest University for Nationalities | Lu H.N.,Northwest University for Nationalities | Zhao Y.M.,Northwest University for Nationalities | Jin N.Z.,Gansu Province Computing Center
Journal of Molecular Modeling | Year: 2017

Apigenin is an important flavonoids due to its antidiabetic bioactivity. It was reported experimentally that the 7-substituent derivative of apigenin has higher biological activity than 4′- and 5-substituted derivatives while introducing sole carboxyalkyl group -(CH2)7COOH into the parent structure. Molecular docking studies indicated that the other two derivatives have lower binding affinities than the 7-substituent derivative (-7.52 kcal mol−1), which is considered to be a better inhibitor than the parent molecule. Almost all of the carbon atoms and oxygen atoms are coplaner for all three molecules in solution phase, however, all carboxyalkyl groups bend inside into the parent molecules in the active site, and the jagged geometries of the carbon chains are destroyed correspondingly. In addition, most of the electron densities of the chemical bonds for all molecules are decreased, especially the 7-substituent derivative. In contrast, most of the Laplacian values for three molecules are increased in the active site, which suggests that the charge densities at the bond critical point (bcp) are much more depleted than the solution phase. Dipole moments of derivatives are all increased in the active site, suggesting strong intermolecular interactions. After interacting with the S. cerevisiae α-glucosidase, only the 7-substituent derivative has the lowest energy gap ΔEHOMO-LUMO, which indicates the lowest stability and the highest inhibition activity. [Figure not available: see fulltext.] © 2017, Springer-Verlag Berlin Heidelberg.


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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