Removal of kinetic traps and enhanced protein folding by strategic substitution of amino acids in a model alpha-helical hairpin peptide.

Abstract:

:The presence of non-native kinetic traps in the free energy landscape of a protein may significantly lengthen the overall folding time so that the folding process becomes unreliable. We use a computational model alpha-helical hairpin peptide to calculate structural free energy landscapes and relate them to the kinetics of folding. We show how protein engineering through strategic changes in only a few amino acid residues along the primary sequence can greatly increase the speed and reliability of the folding process, as seen experimentally. These strategic substitutions also prevent the formation of long-lived misfolded configurations that can cause unwanted aggregations of peptides. These results support arguments that removal of kinetic traps, obligatory or nonobligatory, is crucial for fast folding.

journal_name

Biopolymers

journal_title

Biopolymers

authors

Chapagain PP,Gerstman BS

doi

10.1002/bip.20388

subject

Has Abstract

pub_date

2006-02-15 00:00:00

pages

167-78

issue

3

eissn

0006-3525

issn

1097-0282

journal_volume

81

pub_type

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