Comparative antibacterial analysis of the anthraquinone compounds based on the AIM theory, molecular docking, and dynamics simulation analysis

Abstract

Background: Hydroxyanthraquinones and anthraquinone glucoside derivatives are always considered as the active antibacterial components.

Methods: Comparison of structure characteristics and antibacterial effect of these compounds was performed by applying quantum chemical calculations, atoms in molecules theory, molecular docking, and dynamics simulation procedure. Density functional theory calculation with B3LYP using 6-31G (d, p) basis set has been used to determine ground state molecular geometries.

Results: The molecular geometric stability, electrostatic potential, frontier orbital energies, and topological properties were analyzed at the active site. Once glucose ring is introduced into the hydroxyanthraquinone rings, almost all of the positive molecular potentials are distributed among the hydroxyl hydrogen atoms of the glucose rings. In addition, low electron density ρ (r) and positive Laplacian value of the O-H bond of the anthraquinone glucoside are the evidences of the highly polarized and covalently decreased bonding interactions. The anthraquinone glucoside compounds have generally higher intermolecular binding energies than the corresponding aglycones due to the strong interaction between the glucose rings and the surrounding amino acids. Molecular dynamics simulations further explored the stability and dynamic behavior of the anthraquinone compound and protein complexes through RMSD, RMSF, SASA, and Rg.

Conclusion: The type of carboxyl, hydroxyl, and hydroxymethyl groups on phenyl ring and the substituent glucose rings is important to the interactions with the topoisomerase type II enzyme DNA gyrase B.

Keywords: AIM theory; DFT; Dynamics simulation; Molecular docking; Molecular electrostatic potential.