THE BARRIERS IN PROTEIN-FOLDING

Elimination of an interaction which forms in denatured cytochrome c en ables the majority of the molecules to fold to the native state on a 1 5 ms time scale, without populating observable intermediates. These re sults are contrary to the current view that particular steps in protei n folding, including the supposedly rate-limiting molten globule to na tive transition, are intrinsically slow. Instead it appears that inter mediates characterized so far may be kinetically trapped by barriers t hat are optional rather than integral to the folding process. Major ba rriers may result from misorganization of the chain in the initial con densation step.