The burst phase in ribonuclease A folding and solvent dependence of the unfolded state

Submillisecond hurst phase signals measured in kinetic protein folding experiments have been widely interpreted in terms of the fast formation of productive folding intermediates. Experimental comparisons with non-folding polypeptide chains show that, for ribonuclease A and cytochrome c, these signals in fact reflect a shift from one biased ensemble of the unfolded state to another as a function of change in denaturant concentration.