title: Combined multispectroscopic and molecular dynamics simulation investigation on the interaction between cyclosporine A and β-lactoglobulin.
abstract: β-Lactoglobulin (β-LG), the major whey protein in milks of many mammals, has a high affinity for a wide range of compounds. Cyclosporine A (CsA), is an immunosuppressant drug mainly prescribe in organ transplantation to prevent rejection. In this study, the interaction of CsA with β-LG was investigated using various spectroscopic techniques (UV-visible and fluorescence) in an aqueous medium at two temperatures of 298 and 310K in combination with a molecular dynamics simulation study. The titration results indicated that CsA quenched the fluorescence intensity of β-LG through a static mechanism. The binding constants for the binding of CsA to β-LG at two different temperatures 298 and 310K were obtained 1.12×105and 0.87×105M-1, respectively. Thermodynamic data indicated that the hydrophobic interactions and hydrogen bonds dominate in the binding site. Results of fluorescence resonance energy transfer (FRET) measurements suggest that resonance energy transfer occurs between β-LG and CsA. Moreover, MD simulation results implied that CsA can interact with β-LG, without affecting the secondary structure of β-LG. Experimental and MD simulations data reciprocally supported each other.
authors.affiliation: Department of Chemistry, Faculty of Sciences, Bandar Abbas Branch, Islamic Azad University, Bandar Abbas 7915893144, Iran. Electronic address: fmohsenishahri@gmail.com.
authors.forename: Fatemeh S
authors.initials: FS
authors.lastname: Mohseni-Shahri
authors.affiliation: Department of Chemistry, Faculty of Sciences, Bandar Abbas Branch, Islamic Azad University, Bandar Abbas 7915893144, Iran.
authors.forename: Farid
authors.initials: F
authors.lastname: Moeinpour
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Bizhan
authors.initials: B
authors.lastname: Malaekeh-Nikouei
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hooriyeh
authors.initials: H
authors.lastname: Nassirli
mesh_terms: D001665:Binding Sites; D016572:Cyclosporine / Q000378:metabolism*; D007782:Lactoglobulins / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013057:Spectrum Analysis; D013816:Thermodynamics
chemical_list: D007782:Lactoglobulins; D016572:Cyclosporine
keywords: Absorption spectroscopy; Cyclosporine A; Fluorescence spectroscopy; Molecular dynamics simulation; β-LG