THEORETICAL PREDICTIONS OF FOLDING PATHWAYS BY USING THE PROXIMITY RULE, WITH APPLICATIONS TO BOVINE PANCREATIC TRYPSIN-INHIBITOR

We propose a phenomenological theory that accounts for entropic effect s due to loop formation to predict pathways in the kinetics of protein folding. The theory, the basis of which lies in multiple folding path ways and a three-stage kinetics, qualitatively reproduces most of the kinetic measurements in the refolding of bovine pancreatic trypsin inh ibitor. The resulting pathways show that nonnative kinetic transients are involved in the productive routes leading to the formation of nati ve intermediates. Our theory emphasizes the importance of the random o rigin of chain folding initiation structures in directing protein fold ing.