TY - GEN

T1 - The effects of conformational constraints on aspartic acid racemization

AU - van Duin, Adri C. T.

AU - Collins, Matthew J.

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

KW - Age determination

KW - Collagen

KW - D/L Asp ratio

KW - Molecular dynamics

KW - Molecular mechanics

U2 - 10.1016/S0146-6380(98)00098-9

DO - 10.1016/S0146-6380(98)00098-9

M3 - Conference article

AN - SCOPUS:0032215135

VL - 29

SP - 1227

EP - 1232

JO - Organic Geochemistry

JF - Organic Geochemistry

SN - 0146-6380

IS - 5-7

T2 - 18th International Meeting on Organic Geochemistry

Y2 - 22 September 1997 through 26 September 1997

ER -