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

TitleSlow folding of cross-linked alpha-helical peptides due to steric hindrance
Publication TypeJournal Article
Year of Publication2010
AuthorsPaoli B., Pellarin R., Caflisch A.
JournalThe Journal of Physical Chemistry B
Volume114
Issue5
Pagination2023-2027
Date Published2010 Feb 11
Type of ArticleResearch Article
ISSN1520-5207
KeywordsAmino Acid Sequence, Azo Compounds, Cross-Linking Reagents, Kinetics, Molecular Dynamics Simulation, Molecular Sequence Data, Peptides, Protein Folding, Protein Structure, Secondary, Thermodynamics
Abstract

The folding process of a 16-residue α-helical peptide with an azobenzene cross-linker (covalently bound to residues Cys3 and Cys14) is investigated by 50 molecular dynamics simulations of 4 μs 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.

DOI10.1021/jp910216j
pubindex

0125

Alternate JournalJ. Phys. Chem. B
PubMed ID20088553
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