title: Exploring binding properties of sertraline with human serum albumin: Combination of spectroscopic and molecular modeling studies.
abstract: Human serum albumin (HSA)-drug binding is an important factor to determine half life and bioavailability of drugs. In the present research, the interaction of sertraline (SER) to HSA was investigated using combination of spectroscopic and molecular modeling techniques. Changes in the UV-Vis, CD and FT-IR spectra as well as a significant degree of tryptophan fluorescence quenching were observed upon SER-HSA interaction. Data obtained by spectroscopic methods along with the computational studies suggest that SER binds to residues located in subdomain IIA of HSA. Analysis of spectroscopic data represented the formation of 1:1 complex, significant binding affinity, negative values of entropy and enthalpy changes and the essential role of hydrophobic interactions in binding of SER to HSA. The binding models were demonstrated in the aspects of SER's conformation, active site interactions, important amino acids and hydrogen bonding. Computational mapping of the possible binding site of SER confirmed that the ligand to be bound in a large hydrophobic cavity of HSA. In accordance with experimental data, computational analyses indicated that SER binding does not alter the secondary structure of the protein. The results not only lead to a better understanding of interaction between SER and HSA but also provide useful data about the influence of SER on the protein conformation.
authors.affiliation: Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: mshahlaei@kums.ac.ir.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Shahlaei
authors.affiliation: Students' Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Behnoosh
authors.initials: B
authors.lastname: Rahimi
authors.affiliation: Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Amin
authors.initials: A
authors.lastname: Nowroozi
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Ashrafi-Kooshk
authors.affiliation: Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Komail
authors.initials: K
authors.lastname: Sadrjavadi
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: rkhodarahmi@kums.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Khodarahmi
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D020280:Sertraline / Q000378:metabolism*; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D012709:Serum Albumin; D020280:Sertraline
keywords: Drug binding; Human serum albumin; Ligand–protein interaction; Sertraline