Figure 2.

Convergence of the relative free energies during the geometry optimization for (a) $\mathrm{Fe}{\left({\mathrm{H}}_2\mathrm{O}\right)}_6^{3+}$, (b) $\mathrm{Ru}{\left({\mathrm{H}}_2\mathrm{O}\right)}_6^{3+}$, (c) LC, and (d) RF in QM∕MM-MFEP method. The reduced states of the systems converge similarly as the oxidized states shown here. The vertical dash lines separate different MM ensembles obtained by sequential sampling. Within the region between two dash lines, the dotted lines are the relative free energies of the systems during the QM optimizations on their PMF surfaces in the corresponding MM ensembles. The systems converge after 8–10 cycles of MM sampling and QM optimizations.