What for? Protei, ligand or protein-ligand complex?
You can apply thermodynamic integration or Umbrella sampling (GROMACS) methods for calculation of hydration free energy. It will be complicated enough for a complex, if You will do it alone for the first time. But Justin Lemkul's tutorials will greatly help You in both cases. One problem is that results of MD are highly sensitive to force field that you are going to use and partial charges assignment method (reliable soft or online tool).