How native state topology affects the folding of Dihydrofolate Reductase and Interleukin-1beta

Abstract

The overall structure of the transition state and intermediate ensembles experimentally observed for Dihydrofolate Reductase and Interleukin-1beta can be obtained utilizing simplified models which have almost no energetic frustration. The predictive power of these models suggest that, even for these very large proteins with completely different folding mechanisms and functions, real protein sequences are sufficiently well designed and much of the structural heterogeneity observed in the intermediates and the transition state ensembles is determined by topological effects.