The TIP4P/2005 model was used to represent water molecules . Each PPCP molecule was solvated in a cubic box having an edge length of approx. 25 Å containing ~ 500 water molecules. The aqueous systems were simulated in the NPT ensemble at 1 bar and 300 K using a Nosé-Hover thermo-/barostat with a temperature damping of 100 timesteps and a pressure damping of 1000 timesteps. Three independent trajectories per system were generated. The bonds and angles of the water molecules were held fixed by the SHAKE algorithm. The zeolite-guest systems were simulated in the NVT ensemble at 300 K using a Nosé-Hover thermostat with a damping of 100 timesteps. Five independent trajectories per system were generated. To ensure the absence of autocorrelation all data was resampled prior to evaluation using the timeseries module of pymbar . Example inputs for the insertion and simulated annealing and for the Free Energy Perturbation simulations can be found in the SI, section S7, as well as the code to evaluate the FEP data.