Characterization of the interaction of glycyrrhizin and glycyrrhetinic acid with bovine serum albumin by spectrophotometric-gradient flow injection titration technique and molecular modeling simulations

Publication date: September 2017
Source:International Journal of Biological Macromolecules, Volume 102
Author(s): Firouzeh Manouchehri, Yahya Izadmanesh, Jahan B. Ghasemi
In this research, the interactions of glycyrrhizin (GL) and glycyrrhetinic acid (GA) with bovine serum albumin (BSA) have been investigated by the novel method of spectrophotometric- gradient flow injection titration technique. The hard-modeling multivariate approach to binding was used for calculation of binding constants and estimation of concentration-spectral profiles of equilibrium species. The stoichiometric ratio of binding was estimated using eigenvalue analysis. Results showed that GL and GA bind BSA with overall binding constants of KGL-BSA=3.85 (±0.09)×10⁴Lmol⁻¹, KGA-BSA=3.08 (±0.08)×10⁴Lmol⁻¹. Ligand-BSA complexes were further analyzed by combined docking and molecular dynamics (MD) simulations. Docking simulations were performed to obtain a first guess on the binding structure of the GL/GA-BSA complex, and subsequently analyzed by 20 ns MD simulations in order to evaluate interactions of GL/GA with BSA in detail. Results of MD simulations indicated that GL-BSA complex forms mainly on the basis of hydrogen bonds, while, GA-BSA complex forms on the basis of hydrophobic interactions. Also, water molecules can bridge between the ligand and protein by hydrogen bonds, which are stable during the entire simulation and play an important role in stabilization of the GL/GA-BSA complexes.

Graphical abstract

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2obl8Er
via IFTTT