TABLE 1.

Computed running pK_a values for the blocked histidine from the double- and single-site titration simulations

	0–2 ns	2–4 ns	4–6 ns	6–8 ns	8–10 ns
1	6.8	6.4	7.1	6.8	6.6
2	6.4	7.0	6.6	6.7	6.4
3	6.8	6.5	6.8	6.7	6.8
4	6.9	6.7	6.8	6.6	6.7
5	7.3	7.3	7.3	7.1	6.6
Mean (std.)*	6.8 (0.32)	6.8 (0.37)	6.9 (0.28)	6.8 (0.19)	6.6 (0.15)
ND1†	7.0 (0.45)	7.0 (0.39)	7.0 (0.40)	7.0 (0.48)	7.0 (0.53)
NE2†	6.9 (0.27)	6.8 (0.18)	6.8 (0.19)	6.8 (0.21)	6.8 (0.21)

The pK_a values were obtained from 2-ns time windows with a total simulation time of 10 ns at pH values 6, 7, and 8. An additional 100 ps was allotted for equilibration. A random initial velocity seed was used for each simulation run.

^*Average and standard deviation of pK_a values obtained from five double-site titration simulations.

^†Average and standard deviations of pK_a values obtained from five single-site titration simulations.