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An expanding arsenal of experimental methods yields an explosion of insights into protein folding mechanisms

Abstract

In recent years, improvements in experimental techniques and enhancements in computing power have revolutionized our understanding of the mechanisms of protein folding. By combining insights gained from theory, experiment and simulation we are moving toward an atomistic view of folding landscapes. Future challenges involve exploiting the knowledge gained and methods developed to enable us to elucidate a molecular description of folding dynamics in the complex environment of the cell.

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Figure 1: Schematic representation of folding funnels.
Figure 2: Models of the conformational properties of the ensembles representing the folding intermediates of the bacterial immunity protein Im7 (a; ref. 21) and the rare folding intermediate of the G48V variant of the Fyn SH3 domain24 (b).
Figure 3: Overlapping nucleation motifs in the ribosomal protein S6.

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Acknowledgements

We thank D. Brockwell for critical comments and many helpful insights. We also acknowledge, with grateful thanks, members of our group, our collaborators past and present, and M. Oliveberg and J. Gsponer for their helpful discussions. A.I.B. is supported by the UK Biotechnology and Biological Sciences Research Council (BB/526502/1).

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Bartlett, A., Radford, S. An expanding arsenal of experimental methods yields an explosion of insights into protein folding mechanisms. Nat Struct Mol Biol 16, 582–588 (2009). https://doi.org/10.1038/nsmb.1592

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