title: Stability issues of covalently and noncovalently bonded peptide subunits.
abstract: 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 < or = R2). For noncovalently attached but interacting peptide subunits, such as [For-NH2]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 beta-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 < or = n < or = 8) or the level of theory applied.
authors.affiliation: Department of Organic Chemistry, Eötvös University, P.O. Box 32, H-1518 Budapest 112, Hungary. perczel@chem.elte.hu
authors.forename: András
authors.initials: A
authors.lastname: Perczel
authors.forename: Péter
authors.initials: P
authors.lastname: Hudáky
authors.forename: Anna K
authors.initials: AK
authors.lastname: Füzéry
authors.forename: Imre G
authors.initials: IG
authors.lastname: Csizmadia
mesh_terms: D000409:Alanine / Q000737:chemistry; D000465:Algorithms; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D010455:Peptides; D000409:Alanine