Stability issues of covalently and noncovalently bonded peptide subunits

András Perczel, Péter Hudáky, Anna K. Füzéry, Imre G. Csizmadia

Research output: Contribution to journalArticle

15 Citations (Scopus)


The present study focuses on important questions associated with modeling of peptide and protein stability. Computing at different levels of theory (RHF, B3LYP) for a representative ensemble of conformers of di- and tripeptides of alanine, we found that the Gibbs Free Energy values correlate significantly with the total electronic energy of the molecules (0.922 ≤ R2). For noncovalently attached but interacting peptide subunits, such as [For-NH 2]2 or [For-L-Ala-NH2]2, we have found, as expected, that the basis set superimposition error (BSSE) is large in magnitude for small basis set but significantly smaller when larger basis sets [e.g., B3LYP/6-311++G(d,p)] are used. Stability of the two hydrogen bonds of antiparallel β-pleated sheets were quantitatively determined as a function of the molecular structure, S10 and S14, computed as 4.0 ± 0.5 and 8.1 ± 1.1 kcal/mol, respectively. Finally, a suitable thermoneutral isodesmic reaction was introduced to scale both covalently and noncovalently attached peptide units onto a common stability scale. We found that a suitable isodesmic reaction can result in the total electronic energy as well as the Gibbs free energy of a molecule, from its "noninteracting" fragments, as accurate as a few tenths of a kcal per mol. The latter observation seems to hold for peptides regardless of their length (1≤ n ≤ 8) or the level of theory applied.

Original languageEnglish
Pages (from-to)1084-1100
Number of pages17
JournalJournal of Computational Chemistry
Issue number8
Publication statusPublished - Jun 1 2004


  • Ab initio computation
  • Intermolecular complexes
  • Peptides
  • Protein fragments
  • Structure and stability
  • Thermodynamic functions
  • Thermoneutral isodesmic reaction

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics

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