title: Molecular modeling and spectroscopic studies on the interaction of the chiral drug venlafaxine hydrochloride with bovine serum albumin.
abstract: This study was designed to examine the interaction of racemic antidepressant drug "S,R-venlafaxine hydrochloride (VEN)" with bovine serum albumin (BSA) under physiological conditions. The mechanism of interaction was studied by spectroscopic techniques combination with molecular modeling. Stern-Volmer analysis of fluorescence quenching data shows the presence of the static quenching mechanism. The thermodynamic parameters indicated that the hydrogen bonding and weak van der Waals interactions are the predominant intermolecular forces stabilizing the complex. The number of binding sites (n) was calculated. Through the site marker competitive experiment, VEN was confirmed to be located in subdomain IIIA of BSA. The binding distance (r=4.93 nm) between the donor BSA and acceptor VEN was obtained according to Förster's non-radiative energy transfer theory. According to UV-vis spectra and CD data binding of VEN leaded to conformational changes of BSA. Molecular docking simulations of S and R-VEN revealed that both isomers have similar interaction and the same binding sites, from this point of view S and R isomers are equal.
authors.affiliation: Inorganic Chemistry Department, Faculty of Chemistry, Razi University, Kermanshah, Iran. Electronic address: NahidShahabadi@yahoo.com.
authors.forename: Nahid
authors.initials: N
authors.lastname: Shahabadi
authors.affiliation: Inorganic Chemistry Department, Faculty of Chemistry, Razi University, Kermanshah, Iran.
authors.forename: Saba
authors.initials: S
authors.lastname: Hadidi
mesh_terms: D065966:Absorption, Physicochemical; D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism; D003511:Cyclohexanols / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015203:Reproducibility of Results; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D008024:Ligands; D012710:Serum Albumin, Bovine; D000069470:Venlafaxine Hydrochloride
keywords: Binding mechanism; Bovine serum albumin; Molecular docking; Multi-spectroscopy methods; Protein–drug interaction; Venlafaxine hydrochloride