title: Glutathione--hydroxyl radical interaction: a theoretical study on radical recognition process.
abstract: Non-reactive, comparative (2 × 1.2 μs) molecular dynamics simulations were carried out to characterize the interactions between glutathione (GSH, host molecule) and hydroxyl radical (OH(•), guest molecule). From this analysis, two distinct steps were identified in the recognition process of hydroxyl radical by glutathione: catching and steering, based on the interactions between the host-guest molecules. Over 78% of all interactions are related to the catching mechanism via complex formation between anionic carboxyl groups and the OH radical, hence both terminal residues of GSH serve as recognition sites. The glycine residue has an additional role in the recognition of OH radical, namely the steering. The flexibility of the Gly residue enables the formation of further interactions of other parts of glutathione (e.g. thiol, α- and β-carbons) with the lone electron pair of the hydroxyl radical. Moreover, quantum chemical calculations were carried out on selected GSH/OH(•) complexes and on appropriate GSH conformers to describe the energy profile of the recognition process. The relative enthalpy and the free energy changes of the radical recognition of the strongest complexes varied from -42.4 to -27.8 kJ/mol and from -21.3 to 9.8 kJ/mol, respectively. These complexes, containing two or more intermolecular interactions, would be the starting configurations for the hydrogen atom migration to quench the hydroxyl radical via different reaction channels.
authors.affiliation: Department of Chemical Informatics, Faculty of Education, University of Szeged, Szeged, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Fiser
authors.forename: Balázs
authors.initials: B
authors.lastname: Jójárt
authors.forename: Imre G
authors.initials: IG
authors.lastname: Csizmadia
authors.forename: Béla
authors.initials: B
authors.lastname: Viskolcz
mesh_terms: D005609:Free Radicals / Q000737:chemistry* / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008962:Models, Theoretical; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D005609:Free Radicals; D017665:Hydroxyl Radical; D005978:Glutathione
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