The OpenMM method used c=6 whilst NAMD used c=2, so as such the OpenMM potential is softer. To test if a softer potential in NAMD can alleviate the difference in the TI and FEP calculations, the problematic transformations are repeated using NAMD3 with a soft-core potential with parameters α = 1.0, a = 1, b = 1 and c = 2. Notice that α is modified here because c cannot be set by the user in NAMD. Table shows the resulting ∆∆G values for the repeated calculation and the new differences with the equivalent FEP calculation. The results in table show that there are no remaining significant differences in the TI and FEP result for these transformations. Additionally it can be seen in figure (b) that the gradient no longer features a rapid change in the final state. It should be noted that the choice of α = 1.0 is not a good one and causes an increase in the variance in the final result. Other choices of soft-core parameters should be considered in general .