THERMODYNAMICS OF THE TEMPERATURE-INDUCED UNFOLDING OF GLOBULAR-PROTEINS

The heat capacity, enthalpy, entropy, and Gibbs energy changes for the temperature induced unfolding of 11 globular proteins of known three- dimensional structure have been obtained by microcalorimetric measurem ents. Their experimental values are compared to those we calculate fro m the change in solvent-accessible surface area between the native pro teins and the extended polypeptide chain. We use proportionality coeff icients for the transfer (hydration) of aliphatic, aromatic, and polar groups from gas phase to aqueous solution, we estimate vibrational ef fects, and we discuss the temperature dependence of each constituent o f the thermodynamic functions . Art 25 degrees C, stabilization of the native state of a globular protein is largely due to two favorable te rms: the entropy of nonpolar group hydration and the enthalpy of inter actions within the protein. They compensate the unfavorable entropy ch ange associated with these interactions (conformational entropy) and w ith vibrational effects. Due to the large heat capacity of nonpolar gr oup hydration, its stabilizing contribution decreases quickly at highe r temperatures, and the two unfavorable entropy terms take over, leadi ng to temperature-induced unfolding.