A reassessment of the molecular origin of cold denaturation.

The existence of cold denaturation is now firmly demonstrated by its direct observation for several globular proteins in aqueous solution. But the physico-chemical explanation of this intriguing phenomenon is still unsatisfactory. In this paper we deepen our understanding of cold denaturation by taking advantage of the theoretical model developed by Ikegami and using thermodynamic data on the transfer to water of liquid N-alkyl amides. The analysis leads to the conclusion that the presence of water is fundamental to determine the existence of cold denaturation due to its strong energetic interaction with the amino acid residues previously buried in the protein's interior.