Local versus nonlocal interactions in protein folding and stability--an experimentalist's point of view

One of the classic important issues in protein folding and stability is the relative roles of noncovalent short-range (local) and long-range (nonlocal) interactions. Interest in this topic has been reinforced by recent developments in the analytical theory of protein folding and in lattice-based computer simulations. During the past few years, a wealth of experimental information relevant to this issue has been accumulating. In this review, we focus specifically on experimental aspects, discussing some general ideas that arise from the results obtained by many different groups using a variety of approaches. We also discuss a new experimental strategy that allows us to engineer the contribution of local interactions, and we discuss the first results obtained.