Format

Send to

Choose Destination
J Mol Biol. 2007 Feb 2;365(5):1578-86. Epub 2006 Oct 28.

Transition-states in protein folding kinetics: the structural interpretation of Phi values.

Author information

1
Max Planck Institute of Colloids and Interfaces, Theory Department, 14424 Potsdam, Germany. thomas.weikl@mpikg.mpg.de

Abstract

Phi values are experimental measures of the effects of mutations on the folding kinetics of a protein. A central question is what structural information Phi values give about the transition-state of folding. Traditionally, a Phi value is interpreted as representing the "nativeness" of a mutated residue in the transition-state. However, this interpretation is often problematic. We present here a better structural interpretation of Phi values for mutations within a given helix. Our interpretation is based on a simple physical model that distinguishes between secondary and tertiary free energy contributions of helical residues. From a linear fit of the model to experimental data, we obtain two structural parameters: the extent of helix formation in the transition-state, and the nativeness of tertiary interactions in the transition-state. We apply the model to all proteins with well-characterized helices for which more than 10 Phi values are available: protein A, CI2, and protein L. The model is simple to apply to experimental data, captures nonclassical Phi values <0 or >1 in these helices, and explains how different mutations at a given site can lead to different Phi values.

PMID:
17141267
DOI:
10.1016/j.jmb.2006.10.082
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center