The conformational preference of Cα-centered radicals in proteins

Michael C. Owen, István Komáromi, Richard F. Murphy, Sándor Lovas

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Free radical-induced aggregation of amyloid beta (Aβ) peptide is a recently proposed mechanism in which Cα-centered radicals can form on either Gly33 or Gly29 of Aβ(1-42). Limited structural data for the glycyl radical are available. In this study, the structure of N-Ac-Gly-NHMe and N-Ac-Gly.-NHMe was determined using ab initio and DFT calculations. E=f(φ,ψ) potential energy surfaces (PES) were constructed by independently constraining the φ and ψ angles, 30°apart from 0 to 360°. The structure of each conformer was subsequently optimized using Hartree-Fock and DFT calculations, and the relative energy was calculated using B3LYP/6-31G(d,p). The Poisson-Boltzmann (PB) solver was used to simulate an aqueous environment. The PES of N-Ac-Gly-NHMe was flat, displaying the ability of Gly to sample conformations in both the L and D configurations. Conversely, the N-Ac-Gly.-NHMe had a global minimum in the βL conformation, with a high-energy barrier preventing transitions to other minima. The restricted β conformation of N-Ac-Gly.-NHMe corresponds to the anti-parallel β-sheets observed in Aβ aggregates. The β conformation permits inter-strand H-bonding that could stabilize the aggregates.

Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalJournal of Molecular Structure: THEOCHEM
Volume759
Issue number1-3
DOIs
StatePublished - Feb 14 2006

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Amyloid beta-Peptides
Free Radicals
Conformations
potential energy
proteins
Proteins
Potential energy surfaces
Discrete Fourier transforms
strands
free radicals
peptides
energy
Energy barriers
configurations
Free radicals
Amyloid
Peptides
Agglomeration
N-acetylglycylglycine

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Computational Theory and Mathematics
  • Atomic and Molecular Physics, and Optics

Cite this

The conformational preference of Cα-centered radicals in proteins. / Owen, Michael C.; Komáromi, István; Murphy, Richard F.; Lovas, Sándor.

In: Journal of Molecular Structure: THEOCHEM, Vol. 759, No. 1-3, 14.02.2006, p. 117-124.

Research output: Contribution to journalArticle

Owen, Michael C. ; Komáromi, István ; Murphy, Richard F. ; Lovas, Sándor. / The conformational preference of Cα-centered radicals in proteins. In: Journal of Molecular Structure: THEOCHEM. 2006 ; Vol. 759, No. 1-3. pp. 117-124.
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