title: Protein folding and unfolding in microseconds to nanoseconds by experiment and simulation.
abstract: The Engrailed Homeodomain protein has the highest refolding and unfolding rate constants directly observed to date. Temperature jump relaxation measurements gave a refolding rate constant of 37,500 s(-1) in water at 25 degrees C, rising to 51,000 s(-1) around 42 degrees C. The unfolding rate constant was 1,100 s(-1) in water at 25 degrees C and 205,000 s(-1) at 63 degrees C. The unfolding half-life is extrapolated to be approximately 7.5 ns at 100 degrees C, which allows real-time molecular dynamics unfolding simulations to be tested on this system at a realistic temperature. Preliminary simulations did indeed conform to unfolding on this time scale. Further, similar transition states were observed in simulations at 100 degrees C and 225 degrees C, suggesting that high-temperature simulations provide results applicable to lower temperatures.
authors.affiliation: Medical Research Council Centre for Protein Engineering and Cambridge University Chemical Laboratory, Hills Road, Cambridge CB2 2QH, United Kingdom.
authors.forename: U
authors.initials: U
authors.lastname: Mayor
authors.forename: C M
authors.initials: CM
authors.lastname: Johnson
authors.forename: V
authors.initials: V
authors.lastname: Daggett
authors.forename: A R
authors.initials: AR
authors.lastname: Fersht
mesh_terms: D018398:Homeodomain Proteins / Q000737:chemistry*; D007700:Kinetics; D017510:Protein Folding; D014157:Transcription Factors
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C106185:engrailed homeobox proteins