Conformational microstates entropy

Calculation of entropies of both types is straightforward and efficient because simulations are not required. This allows one to study the conformational stability of many localized microstates of the same molecule by comparison of their harmonic free energies. However, the method is limited only to models of macromolecules in vacuum. 

Even at high temperature, MD simulations with explicit solvent are computationally too expensive to provide meaningful estimates of the conformational entropy of various dominant conformations or microstates. " Approximate entropy values can be obtained on the basis of harmonic or quasiharmonic approximations, or through the use of the more recent local states method. However, while accounting for the conformational entropy, these methods are at present restricted to the analysis of isolated molecules. It is very... 

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