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Eur Biophys J. 2004 Apr;33(2):83-8. Epub 2003 Sep 19.

How do proteins avoid becoming too stable? Biophysical studies into metastable proteins.

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  • 1Department of Biochemistry and Molecular Biology, Monash University, 3800 Clayton, Victoria, Australia.


The vast majority of theoretical and experimental folding studies have shown that as a protein folds, it attempts to adopt a conformation that occurs at its lowest free energy minimum. However, studies on a small number of proteins have now shown that this is a generality. In this review we discuss recent data on how two proteins, alpha-lytic protease and alpha1-antitrypsin, successfully fold to their metastable native states, whilst avoiding more stable but inactive conformations.

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