IMPACT OF LOCAL AND NONLOCAL INTERACTIONS ON THERMODYNAMICS AND KINETICS OF PROTEIN-FOLDING

To address the question of how the geometry of a protein's native conf ormation affects its folding and stability, we studied three model 36- mers on a cubic lattice. The native structure of one of these model 36 -mers consisted mostly of local contacts, while that of a second consi sted mostly of non-local contacts. The third native structure had a ty pical compact native conformation, and served as our reference. For ea ch protein, the amino acid sequence was designed to have a pronounced energy minimum at its native conformation. We observed dramatic differ ences in folding, dependent on the presence or absence of non-local co ntacts. For the proteins with a typical large number of non-local cont acts, the folding transition was all-or-none, whereas for the one with mostly local contacts, it was not. Although the maximum rate of foldi ng was similar for all three proteins, we found that under conditions at which each native conformation was, stable, the structure with most ly non-local contacts folded two orders of magnitude faster than the o ne with mostly local. contacts. The statistical analysis of protein st ructure agrees fully with the implications of the theory. We discuss t he importance of cooperativity in protein folding for its stability. ( C) 1995 Academic Press Limited