Non-Gaussian distributions are observed for the free energies calculated using both TI and MBAR estimators. This assessment of the distribution was made for all 11 transformations of the thrombin target using the OpenMM protocol developed in this work with an ensemble of 48 simulations. The findings of both skewness and kurtosis in the distributions of calculated free energies are consistent with previous work 29 using NAMD2. It was also found, for 6 out of 54 transformations examined with the modified TIES protocols across all MD engines and estimators, that the use of large ensembles of shorter simulations as compared to smaller ensembles of longer simulations could yield comparable accuracy and improved precision.