The difference between states A and B may be in the atom types involved, in which case the ΔF obtained is for "mutating" one molecule onto another, or it may be a difference of geometry, in which case one obtains a free-energy map along one or more reaction coordinates.
Other applications are the virtual screening of ligands in drug discovery, in silico mutagenesis studies[2][3] and antibody affinity maturation.
Umbrella sampling is another free-energy calculation technique that is typically used for calculating the free-energy change associated with a change in "position" coordinates as opposed to "chemical" coordinates, although umbrella sampling can also be used for a chemical transformation when the "chemical" coordinate is treated as a dynamic variable (as in the case of the Lambda dynamics approach of Kong and Brooks).
An alternative to free-energy perturbation for computing potentials of mean force in chemical space is thermodynamic integration.
Adaptations to FEP exist which attempt to apportion free-energy changes to subsections of the chemical structure.