These methods are widely used in ab initio techniques[58] as well as coupled to a Molecular Mechanics force field [59], and they provide valuable information. However they do not give specific interactions between the solute and the bulk. In the case of enzymatic reactivity it is this specificity in the interaction which makes the enzyme so efficient. Sometimes the system is partitioned at different shells, a core and a first sphere of the environment are modeled explicitly while the outer environment is represented by a continuum model[60]. Although there are several methods to model solvent effects in biomolecules [61] with implicit models they will not be commented further.
The second group is the family of methods where the environment is modeled explicitly at a lower computational cost.
These methods are applied successfully to enzymatic reactions [62], to organometallic catalytic processes
[63,64] and to solid state materials such as zeolites [65].
Since these discrete environment methods are used all along this thesis, they will be commented in more detail.