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 language | English |
|---|---|
| Pages (from-to) | 117-124 |
| Number of pages | 8 |
| Journal | Journal of Molecular Structure: THEOCHEM |
| Volume | 759 |
| Issue number | 1-3 |
| DOIs | |
| State | Published - Feb 14 2006 |
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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 journal › Article
}
TY - JOUR
T1 - The conformational preference of Cα-centered radicals in proteins
AU - Owen, Michael C.
AU - Komáromi, István
AU - Murphy, Richard F.
AU - Lovas, Sándor
PY - 2006/2/14
Y1 - 2006/2/14
N2 - 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.
AB - 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.
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U2 - 10.1016/j.theochem.2005.10.047
DO - 10.1016/j.theochem.2005.10.047
M3 - Article
VL - 759
SP - 117
EP - 124
JO - Computational and Theoretical Chemistry
JF - Computational and Theoretical Chemistry
SN - 2210-271X
IS - 1-3
ER -