Linked Life Data

16541426

Source:http://linkedlifedata.com/resource/pubmed/id/16541426

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-3-27
pubmed:abstractText
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, epsilon = 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0192-8651
pubmed:author
pubmed:copyrightInfo
(c) 2006 Wiley Periodicals, Inc.
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
857-67
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
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.
pubmed:affiliation
Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands.
pubmed:publicationType
Journal Article, Comparative Study