As opposed to equal weights, Jarzynsky demonstrated that free energy can be estimated from nonequilibrium-pulling simulations by computing the exponentially averaged work values over the repeats. 103,104 Non-equilibrium techniques do sample multiple pathways and resemble the multiple-US-repeats discussed in this work. However, the US in principle samples an equilibrium distribution, whereas the repeats in the Jarzynsky approach are always outof-equilibrium. Therefore, using exponential averaging may not be directly applicable to the different PMFs of multiple US-repeats. The third possibility is to compute the Boltzmannweighted average of the computed PMF profiles. This weighting approach, however, requires a sufficient overlap of phase spaces between independent US repeats, which most probably is not the case due to the large difference in the computed free energy differences.