title: On the molecular origin of cold denaturation of globular proteins.
abstract: A polypeptide chain can adopt very different conformations, a fundamental distinguishing feature of which is the water accessible surface area, WASA, that is a measure of the layer around the polypeptide chain where the center of water molecules cannot physically enter, generating a solvent-excluded volume effect. The large WASA decrease associated with the folding of a globular protein leads to a large decrease in the solvent-excluded volume, and so to a large increase in the configurational/translational freedom of water molecules. The latter is a quantity that depends upon temperature. Simple calculations over the -30 to 150 °C temperature range, where liquid water can exist at 1 atm, show that such a gain decreases significantly on lowering the temperature below 0 °C, paralleling the decrease in liquid water density. There will be a temperature where the destabilizing contribution of the polypeptide chain conformational entropy exactly matches the stabilizing contribution of the water configurational/translational entropy, leading to cold denaturation.
authors.affiliation: Dipartimento di Scienze Biologiche ed Ambientali, Università del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy. graziano@unisannio.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Graziano
mesh_terms: D003080:Cold Temperature; D008954:Models, Biological; D011489:Protein Denaturation; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins