Table 3.

Efficiency comparison between direct QM∕MM MD and QM∕MM-MFEP methods.

Systemsa	$\mathrm{M}{\left({\mathrm{H}}_2\mathrm{O}\right)}_6^{2∕3+}$		LC∕LC⋅−		RF∕RF⋅−
Total atoms	19		28		47
Basis set	LanL2DZ		6-31+G∗∗		6-31+G∗∗
Number of basis	100		392		613
QM evaluation timeb	3 min		30 min		100 min
Method	Direct	MFEP	Directc	MFEP	Directc	MFEP
Sampling length	20 ps	80 ps	20 ps	80 ps	20 ps	80 ps
QM evaluation number	20 000×6	100×2 d	20 000×6 e	300×2 d	20 000×6 e	300×2 d
Total real timef	40 days	20 days	400 days	25 days	1400 days	45 days

^aM=Fe,Ru.

^bThese are the approximate time costs for a single QM evaluation. The time costs here are based on running GAUSSIAN03 program on dual Intel Xeon 3.60 GHz CPUs.

^cThe direct QM∕MM MD simulations are not performed for LC and RF. The corresponding parameters and time costs are estimations only.

^dThe geometry optimizations are only necessary for the reduced and the oxidized state of solute.

^eAssume using the same setup of simulations as in Ref. 33, where TI method with six sampling intervals is used.

^fThese are the approximate time costs for performing the entire simulations.