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A natural missing link between activated and downhill protein folding scenarios
Physical Chemistry Chemical Physics
  • Feng Liu, University of Illinois at Urbana-Champaign
  • Caroline Maynard, Washington University School of Medicine in St. Louis
  • Gregory E. Scott, University of Illinois at Urbana-Champaign
  • Artem Melnykov, Washington University School of Medicine in St. Louis
  • Kathleen B. Hall, Washington University School of Medicine in St. Louis
  • Martin Gruebele, University of Illinois at Urbana-Champaign
Publication Date
2-1-2010
Abstract

We propose protein PTB1:4W as a good candidate for engineering into a downhill folder. PTB1:4W has a probe-dependent thermal unfolding curve and sub-millisecond T-jump relaxation kinetics on more than one time scale. Its refolding rate in denaturant is a non-linear function of denaturant concentration (curved chevron plot). Yet at high denaturant concentration its unfolding is probe-independent, and the folding kinetics can be fitted to a single exponential decay. The domain appears to fold via a mechanism between downhill folding and activated folding over several small barriers, and when denaturant is added, one of these barriers greatly increases and simplifies the observed folding to apparent two-state kinetics. We predict the simplest free energy function consistent with the thermai denaturation and kinetics experiments by using the singular value Smoluchowski dynamics (SVSD) model. PTB1:4W is a natural 'missing link' between downhill and activated folding. We suggest mutations that could move the protein into the downhill folding limit.

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Citation Information
Feng Liu, Caroline Maynard, Gregory E. Scott, Artem Melnykov, et al.. "A natural missing link between activated and downhill protein folding scenarios" Physical Chemistry Chemical Physics Vol. 12 Iss. 14 (2010) p. 3542 - 3549
Available at: http://works.bepress.com/gscott02/3/