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

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 alpha(1)-antitrypsin, successfully fold to their metastable native states, whilst avoiding more stable but inactive conformations.