Denatured State Effects and the Origin of Nonclassical φ Values in Protein Folding

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