Table 3.
Relative free energy change calculated using alchemical free energy perturbation. Theaflavin digallate is at λ = 0, whereas the mutated residues are at λ = 1. *Using Desmond 2018_4, ** Using Desmond2019_4, ***using Desmond 2018_1.
| Starting molecule, Mutation at λ = 1 | Relative free energy change (kcal/mol) | Core RMSD (In Å) | |
|---|---|---|---|
| FEP1 (test set) | Non-ionized TG, Deletion of four hydroxyl groups | ΔG4 = complex = 8.78+-0.53, ΔG3 = solution = 4.41+-0.39, ΔΔG = 4.38+-0.66 |
0.000 |
| FEP2 (experimental control1) | Non-ionized TG, Deletion of four hydroxyl groups | ΔG4 = complex = 11.12+-0.70, ΔG3 = solution = 5.48+-0.35, ΔΔG = 5.63+-0.78 | 0.790 |
| FEP3 (experimental control2) | Ionized TG, Substitution of two hydroxyl groups with two methyl groups | ΔG4 = complex = 43.61+-0.88, ΔG3 = solution = 41.28+-0.67, ΔΔG = 2.33+-1.11 | 0.000 |
| FEP4 (experimental control3) | Ionized TG, deletion of two hydroxyl groups | ΔG4 = complex = 33.08+-0.91, ΔG3 = solution = 33.65+-0.59, ΔΔG = −0.58+-1.08 | 0.000 |
| FEP5 (experimental control4) | Ionized TG, deletion of four hydroxyl groups | ΔG4 = complex = 163.98+-0.86, ΔG3 = solution = 161.63+-0.54, ΔΔG = 2.35+-1.02 | 0.000 |
| FEP6 (experimental control5) | Ionized TG, deletion of ten hydroxyl groups | ΔG4 = complex = 255.07+-1.63, ΔG3 = solution = 251.18+-1.80, ΔΔG = 3.89+-2.43 | 0.105 |
| FEP7 (experimental control6) | Non-ionized TG, differentially ionized mutated residue, one OH deleted, CH3 added | ΔG4 = complex = −137.65+-8.82, ΔG3 = solution = −141.87+-1.46, ΔΔG = 4.22+-8.94 | 0.356 |
| FEP8 (experimental control7) | Non-ionized TG, differentially ionized mutated residue. Both OH were deleted. | ΔG4 = Complex = − 149.18+-29.98, ΔG3 = solution = −147.13+-1.99, ΔΔG = −2.05+-30.05 | 0.356 |
| FEP9 (experimental control8) | Ionized TG, OH replaced with CH3 | ΔG4 = Complex = 24.32+-3.80 ΔG3 = solution = 20.40+-1.74, ΔΔG = 3.92+-4.18* | Not aligned |
| ΔG4 = Complex = 21.19+-6.51, ΔG3 = solution = 23.30+-3.99, ΔΔG = −2.11+-7.63** | |||
| FEP10 (method control) | CAT-4j, CAT-4b |
ΔG4 = Complex = 30.02+-0.11, ΔG3 = solution = 31.81+-0.04 ΔΔG = −1.79+-0.11*** | Core RMSD: 0.078 |
| ΔG4 = Complex = 30.62+-0.07, ΔG3 = solution = 31.68+-0.03, ΔΔG = −1.06+-0.08** |