The effects of conformational constraints on aspartic acid racemization

Adri C.T. Van Duin, Matthew J. Collins

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40 Scopus citations


In short polypeptides, L-aspartic acid (Asp) and L-asparagine (Asn) can undergo isomerization/deamidation reactions via a succinimide (Asu) intermediate resulting in the formation of D-aspartic acid. Some experimental evidence suggests that this reaction, which has been widely used in age determinations, is severely repressed in structured regions of proteins, like for example the triple-helix of collagen, indicating that conformational constraints imposed on the local peptide geometry by the peptide superstructure may inhibit the formation of Asn-containing sequences relative to Asp- or Asn-containing sequences. To examine this, molecular mechanics and molecular dynamics calculations have been performed on constrained and unconstrained Gly-Pro-Asn-Gly-Pro and Gly-Pro-Asu-Gly-Pro pentapeptides. In the constrained calculations, the influence of the protein helix is simulated by fixing the distance between the backbone-nitrogens in the first and last residue at 11.80 Å, a distance similar to that between comparable atoms in the collagen triple-helix. The results from these simulations show that the constraint significantly destabilizes the Asn-containing pentapeptide relative to the Asn-containing sequence; the molecular dynamics simulations, in which the influence of water was specifically taken into account, predict that the constraint raises the energy difference between these two pentapeptides by 8.8 ± 3.8 kcal/mol. This shows that a protein helical structure may severely repress Asp racemization and Asn deamidation. The conservation of such structures should therefore be taken into consideration when using D/L Asp ratios for age determination.

Original languageEnglish (US)
Pages (from-to)1227-1232
Number of pages6
JournalOrganic Geochemistry
Issue number5-7 -7 pt 2
StatePublished - Nov 1998
EventProceedings of the 1997 18th International Meeting on Organic Geochemistry. Part 2 (of 2) - Maastricht, Neth
Duration: Sep 22 1997Sep 26 1997

All Science Journal Classification (ASJC) codes

  • Geochemistry and Petrology


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