Table 1:
Comparison of calculated pKa’s from replica-exchange and single-pH GBNeck2-CpHMD titrations with experiment, Poisson-Boltzmann and empirical predictionsa
| Protein | PDB | Residue | Expt | Replica | Single pH | H++ | MCCE | DelPhiPKa | PROPKA |
|---|---|---|---|---|---|---|---|---|---|
| Crystal structures | |||||||||
| AGT | 1EH6 | C145 | 5.373 | 6.7 | 6.4±0.01 | 9.5 | 8.3 | 5.3 | 10.6 |
| HMCK | 1I0E | C283 | 5.674 | 5.6 | 6.3±0.13 | 9.1 | 6.8 | 6.0 | 10.4 |
| DJ-1 | 1P5F | C106 | 5.475 | 3.7 | 2.4±0.40 | 11.3 | 12.6 | 6.0 | 12.3 |
| papain | 1PPN | C25 | 3.376 | 4.0 | 3.7±0.05 | 9.3 | 8.8 | 5.6 | 10.5 |
| ppΩ | 1PPO | C25 | 2.976 | 3.7 | 3.1 ±0.12 | 9.4 | 7.6 | 4.9 | 7.5 |
| A1AT | 1QLP | C232 | 6.977 | 7.3 | 6.5±0.08 | 7.3 | 8.3 | 5.5 | 9.1 |
| MmsrA | 2L90 | C72 | 7.278 | 7.9 | 8.2±0.91 | >12.0 | 16.3 | 6.6 | 13.1 |
| AhpC | 4MA9 | C46 | 5.979 | 5.2 | 5.3±0.52 | 9.4 | 9.1 | 5.8 | 9.1 |
| Cathepsin B | 1THE | C29 | 3.660 | - | 3.4±0.02 | 11.2 | - | 6.4 | 11.2 |
| Ubc2 | 1JAS | C88 | 10.280 | - | 9.4±0.55 | 9.8 | - | 6.2 | 9.1 |
| Ubc13 | 1JBB | C87 | 11.180 | - | 11.2±0.07 | 9.3 | - | 6.5 | 9.9 |
| UbcH10C114S | 1I7K | C102 | 10.980 | - | 9.0±0.15 | >12.0 | - | 6.4 | 12.7 |
| RMSE | 0.95 | 1.3(1.1) | |||||||
| R | 0.81 | 0.74(0.92) | |||||||
| Computationally mutated structures | |||||||||
| HMCKS285A | 1I0E | C283 | 6.774 | 9.8 | 9.3±0.12 | 9.3 | 6.6 | 5.9 | 11.2 |
| ACBPM46C | 1NTI | C46 | 8.251 | 7.3 | 7.6±0.15 | 8.8 | 8.8 | 6.6 | 9.0 |
| ACBPS65C | 1NTI | C65 | 9.051 | 7.8 | 8.0±0.05 | 8.8 | 9.4 | 6.7 | 9.6 |
| ACBPT17C | 1NTI | C17 | 9.851 | 10.1 | 10.5±0.03 | 8.4 | 8.8 | 6.4 | 8.9 |
| ACBPV36C | 1NTI | C36 | 9.551 | - | 8.9±0.11 | 9.0 | - | 6.2 | 8.9 |
| ACBPE78C | 1NTI | C78 | 9.651 | - | 11.5±0.18 | 8.7 | - | 6.0 | 9.1 |
| MmsrAE115Q | 2L90 | C72 | 8.278 | 8.7 | 8.0±1.21 | >12.0 | 15.4 | 6.6 | 11.4 |
| MbA125C | 2MGE | C125 | 8.481 | 8.7 | 8.7±0.21 | 8.3 | 8.8 | 6.6 | 9.2 |
| MbG124C | 2MGE | C124 | 6.581 | 8.3 | 8.7±0.06 | 8.1 | 8.5 | 6.0 | 8.4 |
| RMSE | 1.5 | 1.4 (1.3) | |||||||
| R | 0.08 | 0.2 (0.5) | |||||||
| Overall RMSE | 1.2 | 1.3 (1.2) | 3.62 | 4.22 | 2.60 | 4.02 | |||
| Overall R | 0.83 | 0.82(0.89) | −0.48 | 0.23 | 0.61 | −0.10 | |||
The pKa’s from the 4 ns (per replica) replica-exchange and 10 ns (per pH) single pH titrations are listed. For single pH titrations, the RMSE and R values in parentheses include the additional 6 proteins (see main text). For the PB-based H++,18 MCCE,19 and DelPhiPka,20 as well as the empirical PROPKA21 methods, data were taken from the previous publications if available,17,82 or computed with the H++,18 DelPhiPka20 and PDB2PQR83 (for PROPKA21) online servers.