Conserved Nucleation Sites Reinforce the Significance of Phi Value Analysis in Protein-Folding Studies

The only experimental strategy to address the structure of folding transition states, the so-called U value analysis, relies on the synergy between site directed mutagenesis and the measurement of reaction kinetics. Despite its importance, the U value analysis has been often criticized and its power to pin-point structural information has been questioned. In this hypothesis, we demonstrate that comparing the U values between proteins not only allows highlighting the robustness of folding pathways but also provides per se a strong validation of the method. (C) 2014 IUBMB Life, 66(7): 449-452, 2014