title: Molecular ageing: free radical initiated epimerization of thymopentin--a case study.
abstract: The epimerization of amino acid residues increases with age in living organisms. In the present study, the structural consequences and thermodynamic functions of the epimerization of thymopentin (TP-5), the active site of the thymic hormone thymopoietin, were studied using molecular dynamics and density functional theory methods. The results show that free radical-initiated D-amino acid formation is energetically favoured (-130 kJmol(-1)) for each residue and induces significant changes to the peptide structure. In comparison to the wild-type (each residue in the L-configuration), the radius of gyration of the D-Asp(3) epimer of the peptide decreased by 0.5 Å, and disrupted the intramolecular hydrogen bonding of the native peptide. Beyond establishing important structural, energetic and thermodynamic benchmarks and reference data for the structure of TP-5, these results disseminate the understanding of molecular ageing, the epimerization of amino acid residues.
authors.affiliation: Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Dayag
authors.initials: D
authors.lastname: Sheykhkarimli
authors.affiliation: Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Ken-Loon
authors.initials: KL
authors.lastname: Choo
authors.affiliation: Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Owen
authors.affiliation: Department of Chemical Informatics, Faculty of Education, University of Szeged, Boldogasszony sgt. 6, H-6725 Szeged, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Fiser
authors.affiliation: Department of Chemical Informatics, Faculty of Education, University of Szeged, Boldogasszony sgt. 6, H-6725 Szeged, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Jójárt
authors.affiliation: Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Imre G
authors.initials: IG
authors.lastname: Csizmadia
authors.affiliation: Department of Chemical Informatics, Faculty of Education, University of Szeged, Boldogasszony sgt. 6, H-6725 Szeged, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Viskolcz
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry*; D006860:Hydrogen Bonding; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D016305:Thymopentin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D005609:Free Radicals; D010446:Peptide Fragments; D010455:Peptides; D016305:Thymopentin