dorsal/arxiv
View SchemaTransition States in Protein Folding Kinetics: The Structural Interpretation of Phi-values
| Authors | Thomas R. Weikl, Ken A. Dill |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0605048 |
| URL | https://arxiv.org/abs/q-bio/0605048 |
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.
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"abstract": "Phi-values are experimental measures of the effects of mutations on the\nfolding kinetics of a protein. A central question is which structural\ninformation Phi-values contain about the transition state of folding.\nTraditionally, a Phi-value is interpreted as the \u0027nativeness\u0027 of a mutated\nresidue in the transition state. However, this interpretation is often\nproblematic because it assumes a linear relation between the nativeness of the\nresidue and its free-energy contribution. We present here a better structural\ninterpretation of Phi-values for mutations within a given helix. Our\ninterpretation is based on a simple physical model that distinguishes between\nsecondary and tertiary free-energy contributions of helical residues. From a\nlinear fit of our model to the experimental data, we obtain two structural\nparameters: the extent of helix formation in the transition state, and the\nnativeness of tertiary interactions in the transition state. We apply our model\nto all proteins with well-characterized helices for which more than 10\nPhi-values are available: protein A, CI2, and protein L. The model captures\nnonclassical Phi-values \u003c0 or \u003e1 in these helices, and explains how different\nmutations at a given site can lead to different Phi-values.",
"arxiv_id": "q-bio/0605048",
"authors": [
"Thomas R. Weikl",
"Ken A. Dill"
],
"categories": [
"q-bio.BM"
],
"title": "Transition States in Protein Folding Kinetics: The Structural Interpretation of Phi-values",
"url": "https://arxiv.org/abs/q-bio/0605048"
},
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