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Removal of kinetic traps and enhanced protein folding by strategic substitution of amino acids in a model α‐helical hairpin peptide
Author(s) -
Chapagain Prem P.,
Gerstman Bernard S.
Publication year - 2005
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20388
Subject(s) - chemistry , folding (dsp implementation) , protein folding , peptide , amino acid , kinetics , energy landscape , kinetic energy , phi value analysis , sequence (biology) , biophysics , protein engineering , crystallography , biochemistry , enzyme , physics , electrical engineering , biology , engineering , quantum mechanics
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 α‐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. © 2005 Wiley Periodicals, Inc. Biopolymers 81: 167–178, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com