The phenomenon of hydrophobicity can be best understood by combining experimental data and simple, uncomplicated theories not involving many assumptions. Continuing with this approach, it was found in the past year that the large heat capacity change, which is one of the hallmarks of hydrophobicity, is a common response of any liquid upon cavity formation. It was found recently that this small molecule behavior can be extended to protein stability. A simple scheme was found that explains the phenomenon of universal temperatures in protein denaturation thermodynamics. The stability of proteins is found to be due to both the hydrophobic and hydrophophilic parts of the protein, and a quantitative measure was assigned to the relative importance of these two contributions. Future studies will include an accounting for the heat capacity change in protein denaturation. This study is expected to result in being able to construct the whole protein stability curve as a function of temperature and explain the cold as well as the heat denaturation of proteins. It will then give a guidance to protein engineers on what should be done in order to increase the stability of a protein against changes in temperature.
