title: A Comprehensive Computational Study of the Interaction between Human Serum Albumin and Fullerenes.
abstract: Human serum albumin (HSA) is the most abundant blood plasma protein, which transports fatty acids, hormones, and drugs. We consider nanoparticle-HSA interactions by investigating the binding of HSA with three fullerene analogs. Long MD simulations, quantum mechanical (fragment molecular orbital, energy decomposition analysis, atoms-in-molecules), and free energy methods elucidated the binding mechanism in these complexes. Such a systematic study is valuable due to the lack of comprehensive theoretical approaches to date. The main elements of the mechanism include the following: binding to IIA site results in allosteric modulation of the IIIA and heme binding sites with an increase in α-helical structure of IIIA. Fullerenes displayed high binding affinities for HSA; therefore, HSA can be used as a fullerene carrier, facilitating any toxic function the fullerene may exert. Complex formation is driven by hydrogen bonding, van der Waals, nonpolar, charge transfer, and dispersion energy contributions. Proper functionalization of C60 has enhanced its binding to HSA by more than an order of magnitude. This feature may be important for biological applications (e.g., photodynamic therapy of cancer). Satisfactory agreement with relevant experimental and theoretical data has been obtained.
authors.affiliation: Institute of Biology, Pharmaceutical Chemistry and Biotechnology, National Hellenic Research Foundation , 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Leonis
authors.affiliation: Institute of Biology, Pharmaceutical Chemistry and Biotechnology, National Hellenic Research Foundation , 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Aggelos
authors.initials: A
authors.lastname: Avramopoulos
authors.affiliation: Institute of Biology, Pharmaceutical Chemistry and Biotechnology, National Hellenic Research Foundation , 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Konstantinos D
authors.initials: KD
authors.lastname: Papavasileiou
authors.affiliation: Institute of Biology, Pharmaceutical Chemistry and Biotechnology, National Hellenic Research Foundation , 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Heribert
authors.initials: H
authors.lastname: Reis
authors.affiliation: Institut für Physikalische Chemie, KIT , Fritz-Haber Weg 2, 76131 Karlsruhe, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Steinbrecher
authors.affiliation: Institute of Biology, Pharmaceutical Chemistry and Biotechnology, National Hellenic Research Foundation , 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Manthos G
authors.initials: MG
authors.lastname: Papadopoulos
mesh_terms: D037741:Fullerenes / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011789:Quantum Theory; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D037741:Fullerenes; D012709:Serum Albumin