title: An experimental survey of the transition between two-state and downhill protein folding scenarios.
abstract: A kinetic and thermodynamic survey of 35 WW domain sequences is used in combination with a model to discern the energetic requirements for the transition from two-state folding to downhill folding. The sequences used exhibit a 600-fold range of folding rates at the temperature of maximum folding rate. Very stable proteins can achieve complete downhill folding when the temperature is lowered sufficiently below the melting temperature, and then at even lower temperatures they become two-state folders again because of cold denaturation. Less stable proteins never achieve a sufficient bias to fold downhill because of the onset of cold denaturation. The model, considering both heat and cold denaturation, reveals that to achieve incipient downhill folding (barrier <3 RT) or downhill folding (no barrier), the WW domain average melting temperatures have to be >/=50 degrees C for incipient downhill folding and >/=90 degrees C for downhill folding.
authors.affiliation: Center for Biophysics and Computational Biology and Departments of Chemistry and Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Deguo
authors.initials: D
authors.lastname: Du
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Fuller
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Davoren
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Kelly
authors.forename: Martin
authors.initials: M
authors.lastname: Gruebele
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins; D013696:Temperature; D013816:Thermodynamics
chemical_list: D011506:Proteins