Conformation-dependent oH/H2O2 hydrogen abstraction reaction cycles of Gly and Ala residues: A comparative theoretical study

Michael C. Owen, Milán Szóri, Imre G. Csizmadia, Bela Viskolcz

Research output: Article

28 Citations (Scopus)


To determine if OH can initiate the unfolding of an amino acid residue, the elementary reaction coordinates of H abstraction by OH different conformations (βL, γL, γD, αL, and αD) of Gly and Ala dimethyl amides were computed using first-principles quantum computations. The MPWKCIS1K/6-311++G(3df,2p)// BHandHLYP/6-311+G(d,p) level of theory was selected after different combinations of functionals and basis sets were compared. The structures of Gly and Ala in the elementary reaction steps were compared to the conformers of the Gly, Gly, Ala, and Ala structures in the absence of OH/H2O, which were identified by optimizing the minima of the respective potential energy surfaces. A dramatic change in conformation is observed in the Gly and Ala conformers after conversion to Gly and Ala, respectively, and this change can be monitored along the minimal energy pathway. The βL conformer of Gly (-0.3 kJ mol-1) and Ala (-1.6 kJ mol-1) form the lowest-lying transition states in the reaction with OH, whereas the side chain of Ala strongly destabilizes the α conformers compared to the γ conformers, which could cause the lower reactivity shown in Ala. This effect shown in Ala could affect the abstraction of hydrogen from Ala and the other chiral amino acid residues in the helices. The energy of subsequent hydrogen abstraction reactions between Ala and Gly and H2O2 remains approximately 90 kJ mol-1 below the entrance level of the OH reaction, indicating that the OH radical can initiate an α to β transition in an amino acid residue if a molecule such as H 2O2 can provide the hydrogen atom necessary to re-form Gly and Ala. This work delineates the mechanism of the rapid OH- initiated unfolding of peptides and proteins which has been proposed in Alzheimer's and other peptide misfolding diseases involving amyloidogenic peptides.

Original languageEnglish
Pages (from-to)1143-1154
Number of pages12
JournalJournal of Physical Chemistry B
Issue number3
Publication statusPublished - jan. 26 2012

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Fingerprint Dive into the research topics of 'Conformation-dependent <sup>•</sup>oH/H<sub>2</sub>O<sub>2</sub> hydrogen abstraction reaction cycles of Gly and Ala residues: A comparative theoretical study'. Together they form a unique fingerprint.

  • Cite this