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

Clementi, C; Jennings, P A; Onuchic, J N · Proc Natl Acad Sci U S A · 2000

basic_science · Level V

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Abstract

The overall structure of the transition-state and intermediate ensembles observed experimentally for dihydrofolate reductase and interleukin-1beta can be obtained by using simplified models that have almost no energetic frustration. The predictive power of these models suggests 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.

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