Table 1. Submission IDs, names, category, and type for all the pKa prediction sets.
Reference calculations are labeled as nb###. The method name column lists the names provided by each participant in the submission file. The “type” column indicates if a submission was or a post-deadline reference calculation, denoted by “Blind” or “Reference” respectively. The methods in the table are grouped by method category and not ordered by performance.
| Method Category |
Method | Microscopic pKa (Type I) Submission ID |
Macroscopic pKa (Type III) Submission ID |
Submission Type |
Ref. |
|---|---|---|---|---|---|
| DL | Substructure matches to experimental data in pKa OpenEye pKa Prospector Database v1.0 | 5nm4j | Null | [36] | |
| DL | OpenEye pKa-Prospector 1.0.0.3 with Analog Search ion identification algorithm | pwn3m | Null | [36] | |
| LFER | ACD/pKa GALAS (ACD/Percepta Kernel v1.6) | v8qph | 37xm8 | Blind | [37] |
| LFER | ACD/pKa Classic (ACD/Percepta Kernel, v1.6) | xmyhm | Blind | [38] | |
| LFER | Epik Scan (Schrödinger v2017-4) | nb007 | Reference | [30] | |
| LFER | Epik Microscopic (Schrödinger v2017-4) | nb008 | nb010 | Reference | [30] |
| QSPR/ML | OpenEye Gaussian Process | 6tvf8 | hytjn | Blind | [12] |
| QSPR/ML | OpenEye Gaussian Process Resampled | q3pfp | Blind | [12] | |
| QSPR/ML | S+pKa (ADMET Predictor v8.5, Simulations Plus) | hdiyq | gyuhx | Blind | [24] |
| QSPR/ML | Chemicalize v18.23 (ChemAxon MarvinSketch v18.23) | nb015 | Reference | [39] | |
| QSPR/ML | MoKa v3.1.3 | nb016 | nb017 | Reference | [22, 40] |
| QM | Adiabatic scheme with single point correction: SMD/M06-2X//6-311++G(d,p)//M06-2X/6-31+G(d) for bases and SMD/M06-2X//6-311++G(d,p)//M06-2X/6-31G(d) for acids + thermal corrections | ko8yx | ryzue | Blind | [41] |
| QM | Direct scheme with single point correction: SMD/M06-2X//6-311++G(d,p)//M06-2X/6-31+G(d) for bases and SMD/M06-2X//6-311++G(d,p)//M06-2X/6-31G(d) for acids + thermal corrections | w4z0e | xikp8 | Blind | [41] |
| QM | Adiabatic scheme: thermodynamic cycle that uses gas phase optimized structures for gas phase free energy and solution phase geometries for solvent phase free energy. SMD/M06-2X/6-31+G(d) for bases and SMD/M06-2X/6-31G(d) for acids + thermal corrections | wcvnu | 5byn6 | Blind | [41] |
| QM | Vertical scheme: thermodynamic cycle that uses only gas phase optimized structures to compute gas hase and solvation free energy. SMD/M06-2X/6-31+G(d) for bases and SMD/M06-2X/6-31G(d) for acids + Thermal corrections | arcko | w4iyd | Blind | [41] |
| QM | Direct scheme: solution phase free energy is determined by solution phase geometries without thermodynamic cycle SMD/M06-2X/6-31+G(d) for bases and SMD/M06-2X/6-31G(d) for acids + thermal corrections | wexjs | y75vj | Blind | [41] |
| QM + LEC | Jaguar (Schrödinger v2017-4) | nb011 | nb013 | Reference | [42] |
| QM + LEC | CPCM/B3LYP/6-311+G(d,p) and global fitting | y4wws | 35bdm | Blind | [10] |
| QM + LEC | CPCM/B3LYP/6-311+G(d,p) and separate fitting for neutral to negative and for positive to neutral transformations | qsicn | p0jba | Blind | [10] |
| QM + LEC | EC-RISM/MP2/6-311+G(d,p)-P3NI-q-noThiols-2par | kxztt | ds62k | Blind | [43] |
| QM + LEC | EC-RISM/MP2/cc-pVTZ-P2-q-noThiols-2par | ftc8w | 2ii2g | Blind | [43] |
| QM + LEC | EC-RISM/MP2/6-311+G(d,p)-P2-phi-all-2par | ktpj5 | nb001 | Blind* | [43] |
| QM + LEC | EC-RISM/MP2/6-311+G(d,p)-P2-phi-noThiols-2par | wuuvc | nb002 | Blind* | [43] |
| QM + LEC | EC-RISM/MP2/6-311+G(d,p)-P3NI-phi-all-2par | 2umai | nb003 | Blind* | [43] |
| QM + LEC | EC-RISM/MP2/6-311+G(d,p)-P3NI-phi-noThiols-2par | cm2yq | nb004 | Blind* | [43] |
| QM + LEC | EC-RISM/MP2/6-311+G(d,p)-P2-phi-all-1par | z7fhp | nb005 | Blind* | [43] |
| QM + LEC | EC-RISM/MP2/6-311+G(d,p)-P3NI-phi-all-1par | 8toyp | nb006 | Blind* | [43] |
| QM + LEC | EC-RISM/MP2/cc-pVTZ-P2-phi-noThiols-2par | epvmk | ttjd0 | Blind | [43] |
| QM + LEC | EC-RISM/MP2/cc-pVTZ-P2-phi-all-2par | xnoe0 | mkhqa | Blind | [43] |
| QM + LEC | EC-RISM/MP2/cc-pVTZ-P3NI-phi-noThiols-2par | 4o0ia | mpwiy | Blind | [43] |
| QM + LEC | EC-RISM/B3LYP/6-311+G(d,p)-P3NI-q-noThiols-2par | nxaaw | ad5pu | Blind | [43] |
| QM + LEC | EC-RISM/B3LYP/6-311+G(d,p)-P3NI-phi-noThiols-2par | 0xi4b | f0gew | Blind | [43] |
| QM + LEC | EC-RISM/B3LYP/6-311+G(d,p)-P2-phi-noThiols-2par | cywyk | np6b4 | Blind | [43] |
| QM + LEC | PCM/B3LYP/6-311+G(d,p) | gdqeg | yc70m | Blind | [43] |
| QM + LEC | COSMOtherm_FINE17 (COSMOtherm C30_1701, BP/TZVPD/FINE//BP/TZVP/COSMO) | t8ewk | 0hxtm | Blind | [44, 45] |
| QM + LEC | DSD-BLYP-D3(BJ)/def2-TZVPD//PBEh-3c[DCOSMO-RS] + RRHO(GFN-xTB[GBSA]) + Gsolv(COSMO-RS[TZVPD]) and linear fit | xvxzd | Blind | [46] | |
| QM + LEC | ReSCoSS conformations // DSD-BLYP-D3 reranking// COSMOtherm pKa: DSD-BLYP-D3(BJ)/def2-TZVPD// PBE-D3(BJ)/def2-TZVP/COSMO + RRHO[GFN-xTB + GBSA-water] + Gsolv[COSMO-RS(FINE17/TZVPD)] level and COSMOtherm pKa applied at the single conformer pair level (COSMOthermX17.0.5 release and BP-TZVPD-FINE-C30-1701 parameterization) ReSCoSS conformations // COSMOtherm pKa: DSD-BLYP-D3(BJ)/def2-TZVPD// PBE-D3(BJ)/def2-TZVP/COSMO + RRHO[GFN-xTB + GBSA-water] + Gsolv[COSMO-RS(FINE17/TZVPD)] | eyetm | 8xt50 | Blind | [46] |
| QM + LEC | ReSCoSS conformations // COSMOtherm pKa: DSD-BLYP-D3(BJ)/def2-TZVPD// PBE-D3(BJ)/def2-TZVP/COSMO + RRHO[GFN-xTB + GBSA-water] + Gsolv[COSMO-RS(FINE17/TZVPD)] level and COSMOtherm pKa was applied directly on the resulting conformer sets with at least 5% Boltzmann weights for each microspecies (COSMOthermX17.0.5 release and BP-TZVPD-FINE-C30-1701 parameterization) | ccpmw | yqkga | Blind | [46] |
| QM + MM | M06-2X/6-31G*(for bases) or 6-31+G*(for acids) for gas phase, solvation free energy using TI with explicit solvent and GAFF, solvation free energy of proton −265.6 kcal/mol | 0wfzo | Blind | [47] | |
| QM + MM | M06-2X/6-31G*(for bases) or 6-31+G*(for acids) for gas phase, solvation free energy using TI with explicit solvent and GAFF, solvation free energy of proton −271.88 kcal/mol | z3btx | Blind | ||
| QM + MM | M06-2X/6-31G*(for bases) or 6-31+G*(for acids) + thermal state correction for gas phase, solvation free energy using TI with explicit solvent and GAFF, solvation free energy of proton −265.6 kcal/mol | 758j8 | Blind | ||
| QM + MM | M06-2X/6-31G*(for bases) or 6-31+G*(for acids) + thermal state correction for gas phase, solvation free energy using TI with explicit solvent and GAFF, solvation free energy of proton −271.88 kcal/mol | hgn83 | Blind |
*
Microscopic pKa submissions were blind, however, participant requested a correction after blind submission deadline for macroscopic pKa submissions. Therefore, these were assigned submission IDs in the form of nb###.