Back to Search
Start Over
Computational study of ground-state chiral induction in small peptides: Comparison of the relative stability of selected amino acid dimers and oligomers in homochiral and heterochiral combinations
- Source :
- Zhou, Y, Oostenbrink, C, Jongejan, A, van Gunsteren, W F, Hagen, W F, de Leeuw, S W & Jongejan, J A 2006, ' Computational study of ground-state chiral induction in small peptides: comparison of the relative stability of selected amino acid dimers and oligomers in homochiral and heterochiral combinations ', Journal of Computational Chemistry, vol. 27, no. 7, pp. 857-867 . https://doi.org/10.1002/jcc.20378, Journal of Computational Chemistry, 27(7), 857-867. John Wiley and Sons Inc.
- Publication Year :
- 2006
- Publisher :
- Wiley, 2006.
-
Abstract
- The relative stabilities of homochiral and heterochiral forms of selected dipeptides, AA, AS, AC, AV, AF, AD, AK, tripeptides, AAA, AVA, and an acetylpentapeptide, AcGLSFA, have been calculated using thermodynamic integration protocols and the GROMOS 53A6 force field. Integration pathways have been designed that produce minimal disturbance to the system, including the use of soft atoms, low-energy intermediates, and chiral inversion of the smaller amino acid in the peptide. Comparison of the results obtained by thermodynamic integration between the diastereomeric forms (in explicit water, at 300 K) and from exhaustive global minimum-energy searches for the individual dipeptides (implicit water, ε = 78, 0 K) suggests that entropic contributions to the relative stability of the chiral forms are important. This conclusion is supported by the results of explicit calculation of the effect of temperature on the relative stability of alanylvalylalanine diastereomers. The Gibbs free energy calculations predict that at ambient temperature and pressure homochiral dipeptides with small side chains or polar groups in the vicinity of the peptide backbone, AA, AS, and AD, are more stable than their heterochiral counterparts by fractions of a kJ/mol. For bigger side chains, AC, AV, AF, and AK, the heterochiral diastereomers appear to be more stable. Predicted relative stabilities are in line with observations reported in the literature for AE and YY. Excellent agreement is found for the calculated and experimentally determined relative stabilities of the diastereomers of the dipeptide AA and of all-L, AcGLSFA and its diastereomer containing D-serine in the central position. Addition of counterions to the solvent box has no significant effects on charged and neutral forms. From the present findings it would appear unlikely that the intrinsic stability difference between homo- and heterochiral dipeptides has been a driving force in a primordial selection process leading to the incorporation of amino acids with a single enantiomeric configuration in natural proteins. © 2006 Wiley Periodicals, Inc.
- Subjects :
- Models, Molecular
Stereochemistry
Molecular Conformation
Thermodynamic integration
Peptide
Tripeptide
chemistry.chemical_compound
symbols.namesake
Side chain
Computer Simulation
Amino Acids
chemistry.chemical_classification
Dipeptide
Temperature
Diastereomer
Stereoisomerism
General Chemistry
Gibbs free energy
Computational Mathematics
chemistry
symbols
Enantiomer
Peptides
SDG 6 - Clean Water and Sanitation
Dimerization
Subjects
Details
- ISSN :
- 1096987X and 01928651
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Journal of Computational Chemistry
- Accession number :
- edsair.doi.dedup.....3449a061b0a1cfc98b7ba3f17023f3ec