 To imitate a specific nature of molecules, many types of models have been developed.In general, these can be classified by the following three points; (i) the number of interaction points called "site", (ii) whether the model is rigid or flexible, (iii) whether the model includes polarization effects.An alternative to the explicit water models is to use an implicit solvation model, also termed a continuum model, an example of which would be the COSMO solvation model or the polarizable continuum model (PCM) or a hybrid solvation model.