Whilst this procedure describes the simulation protocol accurately, one caveat must be added in the case of the NAMD2 results. The results presented here for NAMD2 are from the work of Bhati et al . In this previous work the gradients, used in equation 2, are collected at intervals of 4 ps but the trajectories are saved at intervals of 10 ps. Therefore, the post-processing of FEP results can only be calculated at intervals of 10 ps. This affects the comparison of TI and FEP results and we address the matter as it arises in the analysis of the results.