Another option is to sample over the binding modes within a given binding free energy calculation, as reviewed elsewhere. Many binding free energy calculations use alchemical techniques where binding free energies are computed by turning off interactions between the ligand and receptor (controlled by an alchemical parameter ), taking the ligand through a nonphysical pathway that allows it to be moved from the binding site to solution, yielding the binding free energy. The Binding Energy Distribution Analysis Method (BEDAM) is one such alchemical method which includes multiple binding modes by allowing the non-interacting or weaklybinding ligand to rearrange and reorient in the binding site before turning back on interactions, thus allowing relatively easy interchange between binding modes in a single set of simulations.