This chapter summarizes the experimental information on protein energetics. This field is developing fast and the concept of the energetics of protein structure has changed considerably during the past few years based on new findings. The proteins which are presented in the chapter are selected from a large number of proteins for which the thermodynamics of unfolding are studied in laboratory. The analysis of protein energetics presented in this chapter is based on several assumptions: (1) protein groups contribute additively, and proportionally as their surfaces, to the overall thermodynamic effects of unfolding; (2) the protein interior closely resembles an organic crystal in the way groups are packed and the energetics of the interactions among these groups are similar to those in the organic crystals; and (3) under certain conditions the denatured protein can be regarded as unfolded. The main criteria in choosing these proteins have been the reversibility of the denaturation process modeling unfolding, the completeness of this unfolding, the reliability of thermodynamic data on this process, and the resolution of the three dimensional structure of the given protein. The latter is important to investigate the correlation between thermodynamic and structural characteristics of protein, including the water-ASA of various groups in the native and unfolded states, the number of hydrogen bonds, and the extent of van der Waals contacts in the native state.
