MM/GBSA binding free energies for CYP2C9 dimers
Calculated binding free energies for top-scored interactions predicted by GRAMM-X for 1R9O bound to CPR, CYP2D6, CYP2C9, and CYP3A4. Values in parentheses are standard deviations. All values are based on at least 50 snapshots from a single trajectory spaced by 10 ps to avoid correlation between models.
| Energy Component | CPR | CYP2D6 | CYP2C9 | CYP3A4 |
|---|---|---|---|---|
| kcal/mol | ||||
| VDW | −124.2 (6.9) | 223.9 (9.9) | −157.5 (6.4) | −115.7 (6.15) |
| EEL | −500.0 (43.2) | −88.9 (28.3) | −224.3 (34.6) | −238.0 (35.3) |
| EGB | 548.2 (38.9) | 249.8 (28.7) | 332.9 (33.5) | 324.7 (32.6) |
| ESURF | −17.23 (0.8) | −28.2 (1.2) | −20.6 (0.7) | −14.5 (0.6) |
| ΔG (gas) | −624.3 (42.0) | −312.7 (32.8) | −381.8 (34.8) | −353.7 (35.3) |
| ΔG (sol) | 531.0 (38.7) | 221.6 (28.0) | 312.4 (33.3) | 310.2 (32.7) |
| ΔG (total) | −93.26 (6.9) | −91.1 (8.2) | −69.4 (5.9) | −43.5 (6.28) |
ΔG (gas), VDW + EEL; ΔG (sol), EGB + ESURF; ΔG (total), ΔG (gas) + ΔG (sol); ΔG (total), binding free energy [(ΔG complex) – (ΔG receptor + ΔG ligand)]; EEL, electrostatic energy; EGB, electrostatic contribution to the solvation free energy calculated by the generalized Born approach; ESURF, nonpolar contribution to the solvation free energy calculated by an empirical model; VDW, van der Waals contribution from the molecular mechanical energy.