Calculations on real proteins (d– f) have considered all possible paths: the folding rate and transition state structure are determined from the lowest free-energy paths. Galzitskaya and Finkelstein and Alm and Baker predicted the folding transition state structure of CheY (f), and CI-2 (d ) and barnase (e), respectively.

The effects of mutations on the folding rate were predicted on the basis of the contribution of the interactions removed by the mutations to the free energy of the transition state ensemble, or by directly determining the change in folding rate. The predicted effects of mutations on the folding rates are shown on the native structure (left); the measured effects, on the right (grey, regions not probed by mutations; experimental results for CI-2 and barnase).


[Next]