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Updated: Jun 19, 2026

Microfluidic Mixers for Studying Protein Folding
Published on: April 10, 2012
Signatures of protein fold switching in the unfolded state
1Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
Abstract:
We have recently shown that, in simulations of unfolded globular proteins, the native contacts are distinguished by their mutual cooperativity, such that this can be used to identify native contact networks. Here, we use this approach to analyze the unfolded states of fold-switching proteins. For a series of designed fold-switching proteins bridging the GA and GB folds, we observe a systematic shift in the networks of cooperative contacts between those of the α and α/β folds. For the naturally occurring fold-switcher RfaH, we also observe that the cooperativities of the contacts corresponding to the alternative folds are much more similar in energy than in the case of the related NusG, which does not switch folds. The results suggest that the signatures of cooperativity of alternative folds encoded by fold-switching sequences are already present in the unfolded state.
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