The effect of newly developed OPLS-AA alanyl radical parameters on peptide secondary structure

Michael C. Owen, László Tóth, Balázs Jojárt, István Komáromi, Imre G. Csizmadia, Bela Viskolcz

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4 Citations (Scopus)


Recent studies using ab initio calculations have shown that C α-centered radical formation by H-abstraction from the backbone of peptide residues has dramatic effects on peptide structure and have suggested that this reaction may contribute to the protein misfolding observed in Alzheimer's and Parkinson's diseases. To enable the effects of C α-centered radicals to be studied in longer peptides and proteins over longer time intervals, force-field parameters for the C α-centered Ala radical were developed for use with the OPLS force field by minimizing the sum of squares deviation between the quantum chemical and OPLS-AA energy hypersurfaces. These parameters were used to determine the effect of the C α-centered Ala radical on the structure of a hepta-alanyl peptide in molecular dynamics (MD) simulations. A negligible sum-of-squares energy deviation was observed in the stretching parameters, and the newly developed OPLS-AA torsional parameters showed a good agreement with the LMP2/cc-pVTZ(-f) hypersurface. The parametrization also demonstrated that derived force-field bond length and bond angle parameters can deviate from the quantum chemical equilibrium values, and that the improper torsional parameters should be developed explicitly with respect to the coupled torsional parameters. The MD simulations showed planar conformations of the C α-containing residue (Alr) are preferred and these conformations increase the formation of γ-, α-, and π-turn structures depending on the position in the turn occupied by the Alr residue. Higher-ordered structures are destabilized by Alr except when this residue occupies position "i + 1" of the 3 10-helix. These results offer new insight into the protein-misfolding mechanisms initiated by H-abstraction from the C α of peptide and protein residues.

Original languageEnglish
Pages (from-to)2569-2580
Number of pages12
JournalJournal of chemical theory and computation
Issue number8
Publication statusPublished - Aug 14 2012

ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry

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