Figure 5.

Comparison between the optimal VI, the approximated VI, and the MVP (minimum variance path)^26,27 at different numbers of sampling states Ñ. (a) One intermediate sampling state. FEP is used to determine the free-energy difference to the end states. In this case, the optimal VI equals the midpoint of the approximated VI. (b) Five sampling states. BAR is used to calculate the free-energy difference between these 5 states. The overall number of sample points is kept constant, i.e., the number of samples per state is lower for a higher number of states. (c) Using 20 sampling states, otherwise the underlying setup is identical to (b).