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Slow folding of cross-linked alpha-helical peptides due to steric hindrance


Paoli, B; Pellarin, R; Caflisch, A (2010). Slow folding of cross-linked alpha-helical peptides due to steric hindrance. Journal of Physical Chemistry. B, 114(5):2023-2027.

Abstract

The folding process of a 16-residue alpha-helical peptide with an azobenzene cross-linker (covalently bound to residues Cys3 and Cys14) is investigated by 50 molecular dynamics simulations of 4 micros each. The folding kinetics at 281 K show a stretched exponential behavior but become simpler and much faster when a distance restraint is used to emulate a nonbulky cross-linker. The free-energy basin of the helical state is divided into two subbasins by a barrier that separates helical conformations with opposite orientations of the Arg10 side chain with respect to the azobenzene cross-linker. In contrast, such barrier is not present in the helical basin of the peptide with the nonbulky cross-linker, which folds with speed similar to the unrestrained peptide. These results indicate that the cross-linker slows down folding because of steric hindrance rather than its restraining effect on the two ends of the helical segment.

The folding process of a 16-residue alpha-helical peptide with an azobenzene cross-linker (covalently bound to residues Cys3 and Cys14) is investigated by 50 molecular dynamics simulations of 4 micros each. The folding kinetics at 281 K show a stretched exponential behavior but become simpler and much faster when a distance restraint is used to emulate a nonbulky cross-linker. The free-energy basin of the helical state is divided into two subbasins by a barrier that separates helical conformations with opposite orientations of the Arg10 side chain with respect to the azobenzene cross-linker. In contrast, such barrier is not present in the helical basin of the peptide with the nonbulky cross-linker, which folds with speed similar to the unrestrained peptide. These results indicate that the cross-linker slows down folding because of steric hindrance rather than its restraining effect on the two ends of the helical segment.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2010
Deposited On:13 Aug 2010 08:27
Last Modified:05 Apr 2016 14:13
Publisher:American Chemical Society
ISSN:1520-5207
Publisher DOI:https://doi.org/10.1021/jp910216j
PubMed ID:20088553
Permanent URL: https://doi.org/10.5167/uzh-35357

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