How native-state topology affects the folding of dihydrofolate reductase and interleukin-1 beta

The overall structure of the transition-state and intermediate ensembles ob served experimentally for dihydrofolate reductase and interleukin-1 beta ca n be obtained by using simplified models that have almost no energetic frus tration, The predictive power of these models suggests that, even for these very large proteins with completely different folding mechanisms and funct ions, real protein sequences are sufficiently well designed, and much of th e structural heterogeneity observed in the intermediates and the transition -state ensembles is determined by topological effects.