title: Characterization of the interaction of glycyrrhizin and glycyrrhetinic acid with bovine serum albumin by spectrophotometric-gradient flow injection titration technique and molecular modeling simulations.
abstract: 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.
authors.affiliation: Faculty of Chemistry, K. N. Toosi University of Technology, Tehran, Iran.
authors.forename: Firouzeh
authors.initials: F
authors.lastname: Manouchehri
authors.affiliation: Faculty of Chemistry, K. N. Toosi University of Technology, Tehran, Iran.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Izadmanesh
authors.affiliation: Faculty of Chemistry, University of Tehran, Tehran, Iran. Electronic address: jahan.ghasemi@ut.ac.ir.
authors.forename: Jahan B
authors.initials: JB
authors.lastname: Ghasemi
mesh_terms: D000818:Animals; D002417:Cattle; D017022:Flow Injection Analysis; D006034:Glycyrrhetinic Acid / Q000378:metabolism*; D019695:Glycyrrhizic Acid / Q000378:metabolism*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D013053:Spectrophotometry
chemical_list: D012710:Serum Albumin, Bovine; D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid
keywords: Binding constant; Gradient flow injection technique; Molecular modeling; Multivariate hard modeling; Serum albumin