Mechanisms of protein folding

The strong correlation between protein folding rates and the contact order suggests that folding rates are largely determined by the topology of the n ative structure. However, for a given topology, there may be several possib le low free energy paths to the native state and the path that is chosen (t he lowest free energy path) may depend on differences in interaction energi es and local free energies of ordering in different parts of the structure. For larger proteins whose folding is assisted by chaperones, such as the E scherichia coli chaperonin GroEL, advances have been made in understanding both the aspects of an unfolded protein that GroEL recognizes and the mode of binding to the chaperonin. The possibility that GroEL can remove non-nat ive proteins from kinetic traps by unfolding them either during polypeptide binding to the chaperonin or during the subsequent ATP-dependent formation of folding-active complexes with the co-chaperonin GroES has also been exp lored.