A thermodynamic approach to the problem of stabilization of globular protein structure: A calorimetric study

The thermal properties of five globular proteins with known spatial structure, ribonuclease, lysozyme, chymotrypsin, cytochrome c and myoglobin, are investigated by scanning microcalorimetry. It is shown that (a) heat-denaturation of these proteins can be described to a first approximation by the two-state transition model; the deviation from this model does not exceed 5% and seems to be due to the existence of highly unstable intermediates; (b) there is an interdependence between the enthalpy and entropy of transition, and the structural parameters of the protein globule (the hydrogen bond content and saturation by contacts between non-polar groups). The Gibbs energy of stabilization of the native structure is determined as a function of temperature.