Table 4.
Microstate ΔG°i4 for SM07 derived from pKas submitted to the SAMPL6 Blind pKa Challenge shows areas of qualitative agreement with significant differences in calculated energies.
|
|
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Microstate |
||||||||||||||
| 0H | 1H | 2H | 3H | 4H | ||||||||||
| ID | 12 | 2 | 3 | 4 | 6 | 7 | 11 | 13 | 14 | 15 | 16 | ΔG16–12 | ΔGcycle | |
|
|
||||||||||||||
| hgn83[25] | NHLBI-9 | 3.7 | 16.7 | 18.0 | 0 | 20.4 | 28.5 | 28.5 | 36.3 | 24.4 | 36.5 | 55.9 | 52.2 | 7.9 |
| 758j8[25] | NHLBI-8 | 8.3 | 12.4 | 17.3 | 0 | 15.8 | 23.9 | 25.6 | 32.6 | 28.8 | 41.1 | 57.4 | 49.1 | 7.9 |
| z3btx[25] | NHLBI-7 | 9.7 | 17.0 | 17.3 | 0 | 14.4 | 23.2 | 21.8 | 30.0 | 18.4 | 30.2 | 49.7 | 40.0 | 8.3 |
| 0wfzo[25] | NHLBI-6 | 14.3 | 15.7 | 16.6 | 0 | 9.8 | 17.2 | 18.6 | 26.1 | 21.8 | 34.2 | 50.8 | 36.5 | 8.3 |
| 8toyp[23] | ECRISM-8 | 20.6 | 6.4 | 5.4 | 0 | −1.4 | −1.3 | 4.5 | 11.6 | 6.6 | 19.9 | 40.7 | 20.1 | 0 |
| arcko[19] | NHLBI-4 | 16.8 | 6.9 | 6.2 | 0 | −6.5 | −2.7 | 6.8 | 12.9 | 4.7 | 20.5 | 36.2 | 19.4 | 0.9 |
| wexjs[19] | NHLBI-5 | 17.8 | 6.8 | 5.9 | 0 | −6.0 | −2.4 | 7.5 | 13.7 | 5.1 | 20.5 | 36.9 | 19.1 | 0.3 |
| w4z0e[19] | NHLBI-2 | 19.0 | 6.7 | 5.8 | 0 | −5.4 | −2.0 | 8.0 | 14.2 | 5.6 | 20.9 | 37.0 | 18.0 | 0.3 |
| wcvnu[19] | NHLBI-3 | 18.1 | 6.8 | 6.5 | 0 | −5.2 | −1.9 | 7.8 | 13.3 | 4.7 | 19.5 | 36.0 | 17.9 | 0.5 |
| ko8yx[19] | NHLBI-1 | 18.0 | 6.9 | 6.5 | 0 | −5.3 | −2.2 | 7.5 | 13.0 | 4.5 | 19.0 | 35.6 | 17.6 | 0.9 |
| z7fhp[23] | ECRISM-7 | 20.2 | 6.3 | 5.4 | 0 | −1.8 | −1.6 | 4.0 | 10.2 | 5.2 | 18.4 | 37.6 | 17.4 | 0 |
| kxztt[23] | ECRISM-1 | 15.9 | 5.4 | 4.1 | 0 | −2.6 | −2.6 | 2.0 | 7.0 | 3.7 | 13.3 | 30.1 | 14.2 | 0 |
| nxaaw[23] | ECRISM-12 | 17.8 | 5.5 | 4.5 | 0 | −4.8 | −4.4 | 5.7 | 8.8 | 0.4 | 14.9 | 30.0 | 12.2 | 0 |
| 2umai[23] | ECRISM-5 | 16.7 | 4.7 | 4.0 | 0 | −2.5 | −2.4 | 1.9 | 5.7 | 2.0 | 11.8 | 25.7 | 9.0 | 0 |
| cm2yq[23] | ECRISM-6 | 16.6 | 4.7 | 4.0 | 0 | −2.5 | −2.4 | 1.8 | 5.7 | 1.9 | 11.8 | 25.6 | 9.0 | 0 |
| epvmk[23] | ECRISM-9 | 14.0 | 4.1 | 3.5 | 0 | −2.9 | −2.7 | 2.7 | 5.5 | 0.7 | 11.0 | 22.8 | 8.8 | 0 |
| 4o0ia[23] | ECRISM-11 | 13.8 | 3.9 | 3.4 | 0 | −2.9 | −2.7 | 2.5 | 5.3 | 0.6 | 10.5 | 22.1 | 8.3 | 0 |
| xnoe0[23] | ECRISM-10 | 14.2 | 4.1 | 3.5 | 0 | −3.1 | −2.9 | 2.5 | 5.1 | 0.2 | 10.5 | 22.1 | 7.9 | 0 |
| ktpj5[23] | ECRISM-3 | 16.5 | 4.7 | 4.0 | 0 | −2.7 | −2.6 | 1.6 | 4.9 | 1.1 | 11.0 | 24.0 | 7.5 | 0 |
| wuuvc[23] | ECRISM-4 | 16.4 | 4.7 | 4.0 | 0 | −2.7 | −2.6 | 1.6 | 4.8 | 1.1 | 10.9 | 23.8 | 7.4 | 0 |
| 0xi4b[23] | ECRISM-13 | 16.7 | 4.6 | 4.4 | 0 | −4.9 | −4.2 | 5.6 | 6.9 | −2.2 | 12.7 | 23.8 | 7.1 | 0 |
| cywyk[23] | ECRISM-14 | 16.3 | 4.5 | 4.3 | 0 | −5.0 | −4.4 | 5.3 | 6.0 | −2.8 | 11.7 | 21.9 | 5.6 | 0 |
| ftc8w[23] | ECRISM-2 | 15.5 | 4.8 | 3.7 | 0 | −4.7 | −4.8 | 1.2 | 2.3 | −2.6 | 7.9 | 18.5 | 3.0 | 0 |
| gdqeg[23] | PCM-15 | 8.9 | 2.9 | 2.4 | 0 | −7.2 | −7.0 | −1.4 | −4.5 | −9.4 | −1.1 | 1.3 | −7.6 | 0 |
| 6tvf8[16] | BannonOE-1 | - | - | - | 0 | −7.1 | −5.1 | −0.5 | −6.3 | −9.5 | −5.9 | −12.9 | NI | 8.8 |
| hdiyq | Rfraczkiewicz | - | - | - | 0 | −5.6 | −3.7 | −1.3 | −5.4 | −2.8 | −2.1 | −1.2 | NI | 0 |
| ccpmw[21] | Wilcken2 | 15.8 | - | - | 0 | −7.4 | −6.0 | 3.4 | - | −7.9 | - | - | NI | NI |
| t8ewk | cosmologic_fine17 | - | - | - | 0 | −7.4 | −5.9 | - | - | - | - | - | NI | NI |
| v8qph | KirilLanevskij-1 | - | - | - | 0 | −5.5 | - | - | - | - | - | - | NI | NI |
| [24] | EPIK | 13.8 | 7.2 | 7.4 | 0 | −5.6 | −3.9 | 0.5 | - | −1.7 | - | - | NI | |
Energy of microstates of SM07 at pH 0, with state 4 used as the reference. ΔG in unitless free energies where a unit change yields a 10-fold population change. Microstate IDs as in Figure 1. The rows are ordered by ΔΔG°16–12, which is the energy difference between the unique 4H and 0H microstates. The tautomers, with the same number of protons are grouped together (1H, 2H, 3H). Energies below zero are indicated in red. ΔG°j4 values are derived from predicted pKas found for the SAMPL6 pKa Challenge: (https://github.com/samplchallenges/SAMPL6/tree/master/physical_properties/pKa/analysis/analysis_of_typeI_predictions/typeI_predictions ). Superscript with the submission ID identifies published papers associated with each submission. Superscript is the reference. The Epik calculations do not have a SAMPL6ID. The only experimentally observed pKa is 6.08 (ΔG°64 = −6.08) is obtained by spectrophotometric method which technically measures the macroscopic pKa for multiprotic molecules. NMR analysis identified microstate state 4 and 6 as dominant microstates that participate in this transition [5]. Values within 1 pH unit of the predicted pKa are underlined. ΔGcycle is the largest difference in energy calculated for the summed ΔG°s along all cycles of length 4 in the graph of SM07 microscopic equilibria for each of the submissions. NI indicates that too few pKas were submitted to generate closed cycles to check for thermodynamic consistency.