Yank 50 (ver 0.20.1) was used to perform binding free energy calculations to compare the free energy differences between the observed toluene binding modes. Three simulations were performed in total. All simulations were run run in the NPT ensemble with a pressure 1 atm at 300K. The coupling for the electrostatics and sterics for each simulation was determined using Yank's auto setting. The first Yank simulation had harmonic restraints in place whose coupling was also determined by the auto setting.