title: Insights into the molecular interaction between two polyoxygenated cinnamoylcoumarin derivatives and human serum albumin.
abstract: Ligand binding studies on human serum albumin (HSA) are crucial in determining the pharmacological properties of drug candidates. Here, two representatives of coumarin-chalcone hybrids were selected and their binding mechanism was identified via thermodynamics techniques, curve resolution analysis and computational methods at molecular levels. The binding parameters were derived using spectroscopic approaches and the results point to only one pocket located near the Trp214 residue in subdomain IIA of HSA. The protein tertiary structure was altered during ligand binding and formed an intermediate structure to create stronger ligand binding interactions. The best binding mode of the ligand was initially estimated by docking on an ensemble of HSA crystallographic structures and by molecular dynamics (MD) simulations. Per residue interaction energies were calculated over the MD trajectories as well. Reasonable agreement was found between experimental and theoretical results about the nature of binding, which was dominated by hydrogen bonding and van der Waals contributions.
authors.affiliation: Institute of Biochemistry and Biophysics and Center of Excellence in Biothermodynamics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran. saboury@ut.ac.ir.
authors.forename: Anahita
authors.initials: A
authors.lastname: Khammari
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Saboury
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Karimi-Jafari
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khoobi
authors.forename: Atiyeh
authors.initials: A
authors.lastname: Ghasemi
authors.forename: Saeed
authors.initials: S
authors.lastname: Yousefinejad
authors.forename: Osama K
authors.initials: OK
authors.lastname: Abou-Zied
mesh_terms: D001665:Binding Sites; D002151:Calorimetry; D002599:Chalcone / Q000737:chemistry; D002942:Circular Dichroism; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000075462:Serum Albumin, Human / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D003374:Coumarins; D002599:Chalcone; C030123:coumarin; D000075462:Serum Albumin, Human