title: Eliminating a Protein Folding Intermediate by Tuning a Local Hydrophobic Contact.
abstract: Intermediate states in protein folding may slow folding, and sometimes can provide a starting point for aggregation. Recently, the FBP28 WW domain of the formin-binding protein was used as a model for a computational study of the origin and prevention of intermediate-state formation, and local hydrophobic interactions of Leu26 were implicated. Here, we combine new simulations over a broad temperature range with experimental temperature-jump data to study this site in more detail. We replace Leu26 by Asp26 or Trp26 to alter the folding scenario from three-state folding toward two-state or downhill folding at temperatures below the melting point, whereas the wild type shows two-state behavior only near its melting temperature. We offer an explanation of this behavior mainly in terms of principles of hydrophobic interactions.
authors: Baker Laboratory of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853-1301, United States.
authors: Khatuna
authors: K
authors: Kachlishvili
authors: Kapil
authors: K
authors: Dave
authors: Martin
authors: M
authors: Gruebele
authors: Baker Laboratory of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853-1301, United States.
authors: Harold A
authors: HA
authors: Scheraga
authors: Baker Laboratory of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853-1301, United States.
authors: Gia G
authors: GG
authors: Maisuradze
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D013696:Temperature
chemical_list: D002352:Carrier Proteins; C473939:formin binding protein 28, human