  Alchemical free energy calculations are a useful tool for predicting free
energy differences associated with the transfer of molecules from one
environment to another. The hallmark of these methods is the use of "bridging"
potential energy functions representing \emph{alchemical} intermediate states
that cannot exist as real chemical species. The data collected from these
bridging alchemical thermodynamic states allows the efficient computation of
transfer free energies (or differences in transfer free energies) with orders
of magnitude less simulation time than simulating the transfer process
directly. While these methods are highly flexible, care must be taken in
avoiding common pitfalls to ensure that computed free energy differences can be
robust and reproducible for the chosen force field, and that appropriate
corrections are included to permit direct comparison with experimental data. In
this paper, we review current best practices for several popular application
domains of alchemical free energy calculations, including relative and absolute
small molecule binding free energy calculations to biomolecular targets.
