# Transition states in protein folding kinetics: Modeling Phi-values of small beta-sheet proteins

Source: [Transition states in protein folding kinetics: Modeling Phi-values of small beta-sheet proteins](<https://www.sota2.com/research/paper/68fa5e991e209131ce9e3b10>)

Collection index: [llms.txt](<https://www.sota2.com/research/llms.txt>)

Data updated: 2025-10-28T13:56:18.930Z

Authors: Thomas R. Weikl

Published: 2007-09-21T09:11:17.000Z

## Abstract

Small single-domain proteins often exhibit only a single free-energy barrier, or transition state, between the denatured and the native state. The folding kinetics of these proteins is usually explored via mutational analysis. A central question is which structural information on the transition state can be derived from the mutational data. In this article, we model and structurally interpret mutational Phi-values for two small beta-sheet proteins, the PIN and the FBP WW domain. The native structure of these WW domains comprises two beta-hairpins that form a three-stranded beta-sheet. In our model, we assume that the transition state consists of two conformations in which either one of the hairpins is formed. Such a transition state has been recently observed in Molecular Dynamics folding-unfolding simulations of a small designed three-stranded beta-sheet protein. We obtain good agreement with the experimental data (i) by splitting up the mutation-induced free-energy changes into terms for the two hairpins and for the small hydrophobic core of the proteins, and (ii) by fitting a single parameter, the relative degree to which hairpin 1 and 2 are formed in the transition state. The model helps to understand how mutations affect the folding kinetics of WW domains, and captures also negative Phi-values that have been difficult to interpret.

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## Original sources and implementation

[Original paper](<https://arxiv.org/abs/0709.3359>)

[PDF](<https://arxiv.org/pdf/0709.3359.pdf>)