Denatured state effects and the origin of nonclassical φ values in protein folding

Analysis of the φ value is one of the most powerful tools to understand the transition state for protein folding. In principle, φ values are expected to fall in the range of 0 to 1. However, a noticeable number of φ values have been observed which are either less than 0 or greater than 1. The origin of such φ values, sometimes referred to as noncanonical or nonclassical φ values, has been controversial. Here we show that mutational effects upon denatured state energetics can lead to nonclassical φ values.