Protein folding from a highly disordered denatured state: The folding pathway of chymotrypsin inhibitor 2 at atomic resolution

Previous experimental and theoretical studies have produced high-resolution descriptions of the native and folding transition states of chymotrypsin i nhibitor 2 (C12), In similar fashion, here we use a combination of NMR expe riments and molecular dynamics simulations to examine the conformations pop ulated by C12 in the denatured state, The denatured state is highly unfolde d, but there is some residual native helical structure along with hydrophob ic clustering in the center of the chain. The lack of persistent nonnative structure in the denatured state reduces barriers that must be overcome, le ading to fast folding through a nucleation-condensation mechanism. With the characterization of the denatured state, we have now completed our descrip tion of the folding/unfolding pathway of CI2 at atomic resolution.