 FEP calculations have been used for studying host–guest binding energetics,
pKa predictions, solvent effects on reactions, and enzymatic reactions.Other applications are the virtual Screening of ligands in drug Discovery, as well as for "In silico" mutagenesis studies.For the
study of reactions it is often necessary to involve a quantum-mechanical (QM) representation of
the reaction center because the molecular mechanics (MM) force fields used for FEP simulations can't handle
breaking bonds.