Additional Methods for Calculating the Entropy

It would be of interest to extend the LS method and the hypothetical scanning method to MC and MD samples of continuum models of fluids (e.g., argon and water) and peptides in aqueous solutions. These methods enable one to calculate differences in free energy between significantly different wide microstates directly—that is, from two samples—and in principle, can handle even small differences in free energy of such microstates because the free energy fluctuations decrease with enhancement of the quality of the approximation. 

In this section we describe several methods not pertaining to the techniques described earlier. We discuss the multicanonical method of Berg as applied to macromolecules, - and the adiabatic switching procedure of Rein-hardt, which is related to the thermodynamic integration approach but is based on different grounds. For completeness, we mention four additional techniques, three of which were developed originally for spin models. 

---