FREE-ENERGY BALANCE IN PROTEIN-FOLDING

This chapter suggests a particular decomposition that relies on classical concepts and that is intuitively straightforward. It aims to provide a semi-quantitative basis for the interpretation of experiments. These include thermodynamic studies of the entire folding process, experiments based on site-directed mutagenesis that attempt to isolate the free energy contributions of individual groups and studies of folding intermediates. A fundamental problem in any attempt at analysis is that the free energy change associated with protein folding is usually described in terms of forces that are much larger than their resultant. The chapter aims to arrive at a model capable of accounting for the small free energy changes that accompany protein folding while providing a more quantitative description of the effects of single-site mutations. The approach is to characterize individual forces by extracting information as to their magnitudes from direct measurements on proteins, from the principles of physical chemistry, and from the methods of continuum electrostatics. The relevant theory and experimental data are discussed individually and an attempt has been made to extract some general principles about protein folding. © 1995, Academic Press Inc.