Alchemical transformations are regularly used to compute free energies of solvation, binding and mutation. The end states of interest are connected by a path using a coupling parameter lambda. The standard procedure is to run multiple simulations, each at a fixed value of lambda, and use Bennett’s acceptance ratio to obtain the free energy difference. In this webinar we present how the Accelerated Weight histogram method can be used for such calculations. In this approach lambda is varied dynamically in a single simulation, and the free energy difference can be obtained directly. This has been implemented in the GROMACS 2021 release and provides a simple and flexible way to compute alchemical free energies and can be trivially parallelized using multiple walkers (copies of the system).