In principle one can calculate all the above thermodynamic observables from a single differential scanning calorimetry thermogram of the system assuming that the  is independent of the temperature. However, it is difficult to obtain accurate values for  this way. More accurately, the  can be derived from the variations in  vs.  which can be achieved from measurements with slight variations in pH or protein concentration. The slope of the linear fit is equal to the . Note that any non-linearity of the datapoints indicates that  is probably not independent of the temperature.
Alternatively, the  can also be estimated from the calculation of the accessible surface area (ASA) of a protein prior and after thermal denaturation as follows:
For proteins that have a known 3d structure, the  can be calculated through computer programs such as Deepview (also known as swiss PDB viewer). The  can be calculated from tabulated values of each amino acid through the semi-empirical equation:
where the subscripts polar, non-polar and aromatic indicate the parts of the 20 naturally occurring amino acids.
Finally for proteins, there is a linear correlation between  and  through the following equation: