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The present view of the mechanism of protein folding

Nature Reviews Molecular Cell Biology volume 4, pages 497–502 (2003)Cite this article

Abstract

We can track the positions and movements of all the atoms in small proteins as they fold and unfold by combining experimental studies with atomic-resolution molecular dynamics simulations. General principles as to how such complex architectures form so rapidly are now emerging from in-depth studies of a few proteins.

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Figure 1: The folding pathway of chymotrypsin inhibitor 2.
Figure 2: The folding pathway of barnase.
Figure 3: The folding pathway of the engrailed homeodomain.
Figure 4: An overlay of transition-state structures from independent unfolding simulations of chymotrypsin inhibitor 2 at different temperatures.
Figure 5: A plot of the logarithm of folding rate constants for various proteins against contact order.

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Acknowledgements

V.D. is grateful for financial support from the National Institutes of Health. A.R.F. is grateful for long-term support from the Medical Research Council. UCSF MidasPlus was used to render the protein structures shown in the figures50.

Author information

Authors and Affiliations

  1. the Department of Medicinal Chemistry, University of Washington, Box 357610, Seattle, 98195–7610, Washington, USA

    Valerie Daggett

  2. Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK

    Alan Fersht

  3. the MRC Centre for Protein Engineering, MRC Centre, Hills Road, Cambridge, CB2 2QH, UK

    Alan Fersht

Authors
  1. Valerie Daggett
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Related links

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DATABASES

InterPro

engrailed homeodomain

fibronectin type III domain

LocusLink

acylphosphatase

titin

Swiss-Prot

barnase

CI2

c-Myb

FURTHER INFORMATION

Valerie Daggett's laboratory

Alan Fersht's laboratory

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Daggett, V., Fersht, A. The present view of the mechanism of protein folding. Nat Rev Mol Cell Biol 4, 497–502 (2003). https://doi.org/10.1038/nrm1126

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