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Stability issues of covalently and noncovalently bonded peptide subunits
Author(s) -
Perczel András,
Hudáky Péter,
Füzéry Anna K.,
Csizmadia Imre G.
Publication year - 2004
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20028
Subject(s) - isodesmic reaction , chemistry , peptide , gibbs free energy , tripeptide , conformational isomerism , crystallography , covalent bond , basis set , structural stability , molecule , computational chemistry , density functional theory , thermodynamics , physics , organic chemistry , biochemistry , structural engineering , engineering
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 ≤ R 2 ). For noncovalently attached but interacting peptide subunits, such as [For‐NH 2 ] 2 or [For‐ L ‐Ala‐NH 2 ] 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. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1084–1100, 2004