The goal of this project is to develop the ability to predict the folding/unfolding behavior of proteins based upon structural information. The physical basis of two fundamental properties of proteins will be addressed, the stability of the native conformation and the cooperativity of the folding/unfolding transition. At the present time, the structure of over five hundred proteins has been determined; also, the thermodynamics of the folding/unfolding behavior of a significant number of proteins has been studied in great detail by high sensitivity calorimetric techniques. Unfortunately, the relationships between protein structure and protein folding behavior are not yet understood at a quantitative level. %%% Understanding the forces and mechanisms that control how proteins fold into their functional structures will significantly advance our knowledge of biological organization at the molecular level. From a practical point of view, the success of this research program will provide a quantitative conceptual framework to improve strategies for the rational design of proteins with specific stability and cooperative properties.
