The effects of conformational constraints on aspartic acid racemization

M.J. Collins; A.C.T. van Duin

doi:10.1016/S0146-6380(98)00098-9

The effects of conformational constraints on aspartic acid racemization

M.J. Collins, A.C.T. van Duin

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Abstract

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 Asu-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 Angstrom, 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 Asu-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. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

Original language	English
Pages (from-to)	1227-1232
Number of pages	5
Journal	Organic Geochemistry
Volume	29
Issue number	5-7
DOIs	https://doi.org/10.1016/S0146-6380(98)00098-9
Publication status	Published - Nov 1998

Bibliographical note

Keywords

D/L Asp ratio
age determination
collagen
molecular mechanics
molecular dynamics
MOLECULAR-DYNAMICS
RESIDUES
ISOMERIZATION
SOLVATION
PROTEINS
CHARGES
WATER

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10.1016/S0146-6380(98)00098-9

http://dx.doi.org/10.1016/S0146-6380(98)00098-9

Cite this

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title = "The effects of conformational constraints on aspartic acid racemization",

abstract = "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 Asu-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 Angstrom, 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 Asu-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. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.",

keywords = "D/L Asp ratio, age determination, collagen, molecular mechanics, molecular dynamics, MOLECULAR-DYNAMICS, RESIDUES, ISOMERIZATION, SOLVATION, PROTEINS, CHARGES, WATER",

author = "M.J. Collins and {van Duin}, A.C.T.",

note = "Copyright {\textcopyright} 1998 Elsevier Science Ltd.",

year = "1998",

month = nov,

doi = "10.1016/S0146-6380(98)00098-9",

language = "English",

volume = "29",

pages = "1227--1232",

journal = "Organic Geochemistry",

issn = "0146-6380",

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TY - JOUR

T1 - The effects of conformational constraints on aspartic acid racemization

AU - Collins, M.J.

AU - van Duin, A.C.T.

PY - 1998/11

Y1 - 1998/11

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 Asu-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 Angstrom, 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 Asu-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. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

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 Asu-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 Angstrom, 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 Asu-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. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

KW - D/L Asp ratio

KW - age determination

KW - collagen

KW - molecular mechanics

KW - molecular dynamics

KW - MOLECULAR-DYNAMICS

KW - RESIDUES

KW - ISOMERIZATION

KW - SOLVATION

KW - PROTEINS

KW - CHARGES

KW - WATER

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

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

M3 - Article

SN - 0146-6380

VL - 29

SP - 1227

EP - 1232

JO - Organic Geochemistry

JF - Organic Geochemistry

IS - 5-7

ER -