Association of complementary fragments and the elucidation of protein folding pathways.

Natural or engineered sites for chemical cleavage can be used to generate complementary fragments of well characterized proteins. The peptide fragments represent a unique tool for studying early events in protein folding, since these are usually the most inaccessible to the experimentalist. Analysis of the isolated fragments in non-denaturing conditions together with the determination of the structure of the folded non-covalent complexes and, most importantly, the kinetic analysis of the resulting second-order association/folding reaction can give a more complete picture of a folding pathway. The contribution of fragments to the understanding of some well characterized protein folding pathways is discussed.