Localized microstates

The coupling of the local microstates into the proper molecular states is provided by the diagonalisation of the spin Hamiltonian matrix. For the zero-field case the diagonalisation matrix represents an orthogonal transformation and its matrix elements relate to the combination of the Clebsch-Gordan coefficients. 

The classical harmonic approximation is adequate at low enough temperatures, where most of the contribution to S. comes from the bottom part of the potential energy well (except near absolute zero, where quantum effects become important " ). This approximation is expected to be less adequate at higher temperatures, where the contribution of the anharmonic wings of a localized microstate become significant. Also, the contribution of the higher frequencies should be calculated quantum mechanically. 

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. 

One needs to describe nonequilibrium phenomena by the simultaneous consideration of mass, temperature, and time of the local states while accounting for the given time and energy dissipation due to temperature changes. The time scale over which microscopic changes occm is much smaller than the time scale associated with macroscopic changes. Temperature fluctuations in a microstate will be different from those in a macroscopic state in which the properties are the averages of many microstate values. 

In this section we describe direct methods— those that enable one to calculate the absolute entropy of localized or wide microstates from a single sample. 

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... 

---