For IBU, the free energy of binding for the down orientation is underestimated by only 0.8 kcal/mol from our simulated result and 1.0 kcal/mol from the experimental result. However, for KET, the error is much larger where the down orientation of our simulated result is -2.3 kcal/mol, the linear model predicts the free energy of binding to be -0.3 kcal/mol.