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HERO ID
4886308
Reference Type
Journal Article
Title
Parameterization of the proline analogue Aze (azetidine-2-carboxylic acid) for molecular dynamics simulations and evaluation of its effect on homo-pentapeptide conformations
Author(s)
Bessonov, K; Vassall, KA; Harauz, G
Year
2013
Is Peer Reviewed?
Yes
Journal
Journal of Molecular Graphics and Modelling
ISSN:
1093-3263
Volume
39
Page Numbers
118-125
Language
English
PMID
23261881
DOI
10.1016/j.jmgm.2012.11.006
Web of Science Id
WOS:000315839400014
Abstract
We have parameterized and evaluated the proline homologue Aze (azetidine-2-carboxylic acid) for the gromos56a3 force-field for use in molecular dynamics simulations using GROMACS. Using bi-phasic cyclohexane/water simulation systems and homo-pentapeptides, we measured the Aze solute interaction potential energies, ability to hydrogen bond with water, and overall compaction, for comparison to Pro, Gly, and Lys. Compared to Pro, Aze has a slightly higher H-bonding potential, and stronger electrostatic but weaker non-electrostatic interactions with water. The 20-ns simulations revealed the preferential positioning of Aze and Pro at the interface of the water and cyclohexane layers, with Aze spending more time in the aqueous layer. We also demonstrated through simulations of the homo-pentapeptides that Aze has a greater propensity than Pro to undergo trans→cis peptide bond isomerization, which results in a severe 180° bend in the polypeptide chain. The results provide evidence for the hypothesis that the misincorporation of Aze within proline-rich regions of proteins could disrupt the formation of poly-proline type II structures and compromise events such as recognition and binding by SH3-domains.
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