Alongside using large equilibrium molecular simulations to estimate binding free energy, alchemical methods promise to directly estimate the binding free energy (∆G) of inhibitor binding. These absolute binding free energy calculations can also be used to compute relative binding free energies (∆∆G), ranking ligands by their relative efficacies to one another. Both absolute and relative binding free energies, and particularly relative, have shown great promise in modern drug design campaigns to enable the design of new inhibitors .