title: Consequences of localized frustration for the folding mechanism of the IM7 protein.
abstract: In the laboratory, IM7 has been found to have an unusual folding mechanism in which an "on-pathway" intermediate with nonnative interactions is formed. We show that this intermediate is a consequence of an unusual cluster of highly frustrated interactions in the native structure. This cluster is involved in the binding of IM7 to its target, Colicin E7. Redesign of residues in this cluster to eliminate frustration is predicted by simulations to lead to faster folding without the population of an intermediate ensemble.
authors: Department of Physics, University of Milan, Via Celoria 16, 20133 Milan, Italy.
authors: Ludovico
authors: L
authors: Sutto
authors: Joachim
authors: J
authors: Lätzer
authors: Joseph A
authors: JA
authors: Hegler
authors: Diego U
authors: DU
authors: Ferreiro
authors: Peter G
authors: PG
authors: Wolynes
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019295:Computational Biology; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D017510:Protein Folding; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013816:Thermodynamics
chemical_list: D002352:Carrier Proteins; C509253:E colicin-binding immunity protein Im7, E coli; D029968:Escherichia coli Proteins