Table 3b:

Epik SM07 microstate standard state free energies

state	Δmj,4	ΔG°j,4	source	ΔG°’j,4
12	−1	13.77	pK12,4	6.77
2	0	5.8 8.63	ΔG°6,4-ΔG°6,2 ΔG°12,4-ΔG°12,2	5.8 8.63
3	0	7.15 7.67	ΔG°7,4-ΔG°7,3 ΔG°12,4-ΔG°12,3	7.15 7.67
4	0	0	reference	0
6	1	−5.6	pK6,4	1.4
7	1	−3.88	pK7,4	3.12
11	1	0.47	pK11,4	7.47
14	2	−1.71	ΔG°14,7 + ΔG°7,4	12.29

Table 3a:. pK_a are obtained from [24]. Microstate j has one more proton than microstate k. ΔG°_jk is the free energy difference between states j and k at pH 0 (eqn 2b). State IDs are given in Figure 1 and 3b. Table 3b: Δm_j,4 is the change in the number of protons relative to state 4. ΔG°_j4 and ΔG°’_j4 are the relative microstate free energy at pH 0 and 7 respectively. Source: Where pK_j,k is indicated equation 2b and table 3a are used; otherwise the ΔG°s listed are summed to generate the energy difference between the desired microstate and microstate 4 using the network in Figure 3b.The energy of microstates 2 and 3 are obtained from the sum of the free energies around the indicated loop using the path described and the resultant ΔG° is the average of the two paths. ΔG presented as unitless free energies where a unit change in ΔG yields a 10-fold population change.