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From Figure 3 b it can be seen that the probability distributions of the two ensembles have very little overlap. In terms of efficiency of a FEP simulation with the Zwanzig equation, however, it would have been much better to reverse the ordering (1 is mapped to 46, 2 to 45,..). This mapping would result in a much better overlap of the probability distributions, and consequently in a much smaller variance of the free energy estimate obtained from such a simulation. (11, 14, 15, 20)
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