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Competitive pathways for peptide deamidation

Saron Catak UGent, Bart De Sterck UGent, RE Bulo, Michel Waroquier UGent and Veronique Van Speybroeck UGent (2011) Ninth triennial congress of the World Association of Theoretical and Computational Chemists, WATOC 2011. p.104-104
abstract
Asparagine (Asn) residues spontaneously – yet non-enzymatically – deamidate to form aspartate under physiological conditions, causing time-dependent changes in the conformation of proteins, limiting their lifetime [1]. The 'molecular clocks' hypothesis [2], suggests that deamidation is a biological molecular timing mechanism that could be set to any desired time interval by genetic control of the protein structure and the immediate environment of the Asn residue. The fact that deamidation occurs over a wide range of biologically relevant time intervals suggests that different mechanisms may be at play. To date deamidation is believed to occur over a succinimide-mediated pathway [3]. A novel route leading to the succinimide intermediate via tautomerization of the Asn side chain amide functionality was recently proposed [4,5]. The current study introduces a new 'competing' route for the deamidation of asparagine residues. The aim is to comparatively analyze the feasibility of this new mechanism against the traditional succinimide route, taking into account the catalytic effect of the solvent environment. For this purpose, QM dynamics and meta-dynamics calculations were performed on a model peptide placed in a periodic water box. These results will identify the lowest energy pathway for asparagine deamidation and will serve as a stepping stone for QM/MM calculations of Asn deamidation in proteins.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
published
subject
in
Ninth triennial congress of the World Association of Theoretical and Computational Chemists, WATOC 2011
article_number
abstract PIII 104
pages
104 - 104
conference name
9th Triennial congress of the World Association of Theoretical and Computational Chemists (WATOC 2011)
conference location
Santiago de Compostela, Spain
conference start
2011-07-17
conference end
2011-07-22
language
English
UGent publication?
yes
classification
C3
copyright statement
I have transferred the copyright for this publication to the publisher
id
1946475
handle
http://hdl.handle.net/1854/LU-1946475
date created
2011-11-22 12:25:39
date last changed
2011-11-25 09:42:42
@inproceedings{1946475,
  abstract     = {Asparagine (Asn) residues spontaneously -- yet non-enzymatically -- deamidate to form aspartate under physiological conditions, causing time-dependent changes in the conformation of proteins, limiting their lifetime [1]. The 'molecular clocks'  hypothesis [2], suggests that deamidation is a biological molecular timing mechanism that could be set to any desired time interval by genetic control of the protein structure and the immediate environment of the Asn residue. The fact that deamidation occurs over a wide range of biologically relevant time intervals suggests that different mechanisms may be at play. To date deamidation is believed to occur over a succinimide-mediated pathway [3]. A novel route leading to the succinimide intermediate via tautomerization of the Asn side chain amide functionality was recently proposed [4,5]. The current study introduces a new 'competing' route for the deamidation of asparagine residues.  The aim is to comparatively analyze the feasibility of this new mechanism against  the traditional succinimide route, taking into account the catalytic effect of the solvent environment. For this purpose, QM dynamics and meta-dynamics calculations  were performed on a model peptide placed in a periodic water box. These results will identify the lowest energy pathway for asparagine deamidation and will serve as a stepping stone for  QM/MM calculations of Asn deamidation in proteins.},
  articleno    = {abstract PIII 104},
  author       = {Catak, Saron and De Sterck, Bart and Bulo, RE and Waroquier, Michel and Van Speybroeck, Veronique},
  booktitle    = {Ninth triennial congress of the World Association of Theoretical and Computational Chemists, WATOC 2011},
  language     = {eng},
  location     = {Santiago de Compostela, Spain},
  pages        = {abstract PIII 104:104--abstract PIII 104:104},
  title        = {Competitive pathways for peptide deamidation},
  year         = {2011},
}

Chicago
Catak, Saron, Bart De Sterck, RE Bulo, Michel Waroquier, and Veronique Van Speybroeck. 2011. “Competitive Pathways for Peptide Deamidation.” In Ninth Triennial Congress of the World Association of Theoretical and Computational Chemists, WATOC 2011, 104–104.
APA
Catak, S., De Sterck, B., Bulo, R., Waroquier, M., & Van Speybroeck, V. (2011). Competitive pathways for peptide deamidation. Ninth triennial congress of the World Association of Theoretical and Computational Chemists, WATOC 2011 (pp. 104–104). Presented at the 9th Triennial congress of the World Association of Theoretical and Computational Chemists (WATOC 2011).
Vancouver
1.
Catak S, De Sterck B, Bulo R, Waroquier M, Van Speybroeck V. Competitive pathways for peptide deamidation. Ninth triennial congress of the World Association of Theoretical and Computational Chemists, WATOC 2011. 2011. p. 104–104.
MLA
Catak, Saron, Bart De Sterck, RE Bulo, et al. “Competitive Pathways for Peptide Deamidation.” Ninth Triennial Congress of the World Association of Theoretical and Computational Chemists, WATOC 2011. 2011. 104–104. Print.