Table 1.
Free-energy changes for simulated mutations (kcal/mol)
| Mutation | Trypsin | Thrombin | uPA | Water* |
|---|---|---|---|---|
| Results of simulations by using QMPFF3 force field | ||||
| 1→2 | 5.3 (3) | 8.1 (3) | 4.0 (2) | 3.2 (2) |
| 2→1 | −5.6 (3) | −7.7 (2) | ||
| 2→3 | 1.9 (3) | 0.7 (3) | 2.2 (3) | 0.2 (4) |
| 3→4 | −6.8 (3) | −7.9 (4) | −5.0 (2) | −4.6 (2) |
| 4→3 | 7.9 (2) | |||
| 4→1 | −0.7 (3) | −1.2 (3) | −0.8 (2) | 1.3 (3) |
| 1→5† | −4.0 (4) | −5.7 (5) | −4.3 (4) | −7.7 (5) |
| Results of simulations by using MMFF force field | ||||
| 1→2 | −3.2 (3) | 2.6 (3) | −1.8 (2) | −4.3 (2) |
| 2→3 | −6.2 (2) | −7.4 (2) | −5.1 (2) | −5.7 (2) |
| 3→4 | 3.6 (2) | −1.0 (3) | 2.0 (2) | 5.0 (2) |
| 4→3 | −3.9 (2) | |||
| 4→1 | 5.7 (2) | 5.5 (2) | 4.5 (2) | 5.0 (2) |
| 1→5† | −28.3 (4) | −36.4 (9) | −27.8 (4) | −28.9 (4) |
*With account for correction on different charge states of the ligands in complexes and in solution as described in SI Text, Thermodynamical Cycle Approach When Ligands Are in Different Charged States in Different Environments.
†With account for NVT-NPT correction as described in SI Text, Introduction of NVT-NPT Correction.