Phi-values in protein folding kinetics have energetic and structural components

Abstract

Phi-values are experimental measures of how the kinetics of protein folding is changed by single-site mutations. Phi-values measure energetic quantities, but are often interpreted in terms of the structures of the transition state ensemble. Here we describe a simple analytical model of the folding kinetics in terms of the formation of protein substructures. The model shows that Phi-values have both structural and energetic components. In addition, it provides a natural and general interpretation of "nonclassical" Phi-values (i.e., less than zero, or greater than one). The model reproduces the Phi-values for 20 single-residue mutations in the alpha-helix of the protein CI2, including several nonclassical Phi-values, in good agreement with experiments.

15 pages, 3 figures, 1 table

References in corpus (3)

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• Microscopic Theory of Protein Folding Rates.I: Fine Structure of the Free Energy Profile and Folding Routes from a Variational Approach
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Cited by in corpus (6)

• Identifying critical residues in protein folding: Insights from phi-value and Pfold analysis
• Transition states in protein folding kinetics: Modeling Phi-values of small beta-sheet proteins
• Transition states in protein folding
• Transition States in Protein Folding Kinetics: The Structural Interpretation of Phi-values
• On the relation between native geometry and conformational plasticity
• Loop-closure principles in protein folding