Misconceptions arising from a Sign Discrepancy in Thermodynamic Data for the Gibbs Free Energy Profile of Ribonuclease A

An apparent discrepancy in the data for the Gibbs free energy change as a function of temperature at different pHs, originally published by Brandts in 1965 and repeated by Brandts and Hunt in 1967 with an unexplained change in sign, has lead to close to 40 years of misguided thinking in examining the thermodynamics of protein unfolding, including the frequently promulgated idea of cold denaturation. We have carried out a detailed analysis based on the Planck-Benzinger approach, which is very powerful in clarifying the fundamental aspects of biochemical energetics.