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Title: Molecular ageing: Free radical initiated epimerization of thymopentin – A case study

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{sup −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{sup 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:
;  [1] ; ;  [1] ;  [2] ;  [3] ;  [2] ; ;  [4] ;  [2] ;  [4] ;  [3] ;  [2]
  1. Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6 (Canada)
  2. (Hungary)
  3. (GIOCOMMS), Szentkirályi utca 47, H-1088 Budapest (Hungary)
  4. Department of Chemical Informatics, Faculty of Education, University of Szeged, Boldogasszony sgt. 6, H-6725 Szeged (Hungary)
Publication Date:
OSTI Identifier:
22304382
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Chemical Physics; Journal Volume: 140; Journal Issue: 20; Other Information: (c) 2014 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; AMINO ACIDS; BONDING; DENSITY FUNCTIONAL METHOD; HYDROGEN; MOLECULAR DYNAMICS METHOD; PEPTIDES; RADICALS; RESIDUES