Quantum chemical analysis of the unfolding of a penta-glycyl 3(10)-helix initiated by HO\centerdot, HO(2)\centerdot, and O(2)-\centerdot

TitleQuantum chemical analysis of the unfolding of a penta-glycyl 3(10)-helix initiated by HO\centerdot, HO(2)\centerdot, and O(2)-\centerdot
Publication TypeJournal Article
Year of Publication2011
AuthorsOwen MC, Viskolcz B, Csizmadia IG
JournalJournal of Chemical Physics
Volume135
Date PublishedJUL 21
ISSN0021-9606
Abstract

In this study, the thermodynamic functions of hydrogen abstraction from the C a and amide nitrogen of Gly(3) in a homo-pentapeptide (N-Ac-GGGGG-NH(2); G5) by HO(center dot), HO(2)(center dot), and O(2)(-center dot) were computed using the Becke three-parameter Lee-Yang-Parr (B3LYP) density functional. The thermodynamic functions, standard enthalpy (Delta H degrees), Gibbs free energy (Delta G degrees), and entropy (Delta S degrees), of these reactions were computed with G5 in the 3(10)-helical (G5(Hel)) and fully-extended (G5(Ext)) conformations at the B3LYP/6-31G(d) and B3LYP/6-311+G(d,p) levels of theory, both in the gas phase and using the conductor-like polarizable continuum model implicit water model. H abstraction is more favorable at the C(alpha) than at the amide nitrogen. The secondary structure of G5 affects the bond dissociation energy of the H-C(alpha), but has a negligible effect on the dissociation energy of the H-N bond. The HO(center dot) radical is the strongest hydrogen abstractor, followed by HO(2)(center dot), and finally O(2)(-center dot). The secondary structure elements, such as H-bonds in the 3(10)-helix, protect the peptide from radical attack by disabling the potential electron delocalization at the C(alpha), which is possible when G5 is in the extended conformation. The unfolding of the peptide radicals is more favorable than the unfolding of G5(Hel); however, only the HO(center dot) can initiate the unfolding of G5(Hel) and the formation of G5(Ext)(center dot). These results are relevant to peptides that are prone to undergoing transitions from helical structures to beta-sheets in the cellular condition known as ``oxidative stress{''} and the results are discussed in this context. (C) 2011 American Institute of Physics. {[}doi: 10.1063/1.3608168]

DOI10.1063/1.3608168