It can be said that for all the methods mentioned above, the objective is to provide predictive accuracy within the same range as that reached by experiment (i.e., < 0.2 pK units). A perfect method ought to be system-independent and hence not require fitting to experimental data. It should be able to robustly predict the free energies of protonation in the core of a protein as well as in the solvent-exposed regions, which requires that solute-solvent interactions be accurately represented. Moreover, the ability to change the environmental conditions (e.g., temperature and ionic concentration) is another necessary requirement.