The goals of this proposal follow two parallel developments in the application of thermodynamics to problems of protein unfolding. One addresses fundamental issues associated with thermodynamics of solvent-induced and thermal unfolding of proteins and the other involves the use of thermodynamic techniques in studies of the unfolding of oxidized and reduced thioredoxin and mutant thioredoxin species. Thioredoxin is a protein in which a change in protein stability is an integral aspect of it function. Thermodynamic studies of the unfolding of thioredoxin and site-specific mutant forms of this protein can be used to establish the ground rules and constraints to which mechanistic studies of thioredoxin folding must conform. Historically, there have been two major approaches to the problem of protein folding. One, largely thermodynamic in emphasis, is concerned with the stability of protein species and attempts to understand the forces which lead to stabilization of the native (folded) state. The other approach, which uses kinetic studies to a large extent, focuses on mechanisms of folding with the goal of understanding the molecular events which ultimately lead to the folding native protein. Both of these approaches have contributed to the present day understanding of protein folding.
