Removal of kinetic traps and enhanced protein folding by strategic substitution of amino acids in a model alpha-helical hairpin peptide.
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.
Chapagain
Prem P
PP
Department of Physics, Florida International University, University Park, Miami, FL 33199, USA.
Gerstman
Bernard S
BS
D019943:Amino Acid Substitution / Q000502:physiology*; D003198:Computer Simulation; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary / Q000502:physiology; D013816:Thermodynamics; D013997:Time Factors
D010455:Peptides