# Transition States in Protein Folding Kinetics: The Structural Interpretation of Phi-values Source: [Transition States in Protein Folding Kinetics: The Structural Interpretation of Phi-values]() Collection index: [llms.txt]() Data updated: 2025-10-25T18:51:47.974Z Authors: Thomas R. Weikl, Ken A. Dill Published: 2006-05-30T10:04:49.000Z ## Abstract Phi-values are experimental measures of the effects of mutations on the folding kinetics of a protein. A central question is which structural information Phi-values contain about the transition state of folding. Traditionally, a Phi-value is interpreted as the 'nativeness' of a mutated residue in the transition state. However, this interpretation is often problematic because it assumes a linear relation between the nativeness of the residue and its free-energy contribution. 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 our model to the 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 our 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 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. ## Recorded benchmark results A research result applies to its stated dataset, split, metric and evaluation configuration. Compare like-for-like settings, preserve the metric's unit and direction, and distinguish paper-reported results from independent reproduction. The best result recorded here is not a claim of exhaustive, current global coverage. ## Original sources and implementation [Original paper]() [PDF]()