Table 2.
Binding free energy components of protein-protein and protein-ligand complexes (in kcal/mol units)
| System | ΔEvdw | ΔEele | ΔGele,sol | ΔGnpol,sol | ΔEnon-polar | ΔEpolar | ΔGbind |
|---|---|---|---|---|---|---|---|
| Protein-protein Free and bound wild type KRas4B-PDE6δ complex | |||||||
| KRas4B-PDE6δ | − 123.08 (0.35) | − 1546.94 (4.40) | 1608.17 (4.25) | −17.78 (0.04) | − 140.86 | 61.23 | −79.63 (0.43) |
| KRas4B-PDE6δ-D14 | − 124.99 (0.44) | − 1127.75 (3.74) | 1187.01 (3.50) | − 18.26 (0.05) | − 143.25 | 59.26 | −83.99 (0.42) |
| KRas4B-PDE6δ-C22 | − 142.17 (0.40) | − 1113.87 (4.30) | 1185.59 (4.11) | −20.62 (0.03) | − 162.79 | 71.72 | −91.07 (0.38) |
| Free and bound mutated KRas4BG12C-PDE6δ | |||||||
| KRas4BG12C-PDE6δ | −127.74 (0.51) | − 1507.30 (5.58) | 1550.55 (5.31) | −18.85 (0.06) | − 146.59 | 43.25 | − 103.34 (0.77) |
| KRas4BG12C-PDE6δ-D14 | −124.12 (0.51) | − 1083.80 (6.00) | 1142.97 (5.68) | −18.00 (0.05) | −142.12 | 59.17 | −82.95 (0.68) |
| KRas4BG12C-PDE6δ-C22 | − 126.67 (0.39) | − 1550.02 (3.88) | 1587.85 (3.75) | −18.86 (0.05) | − 145.53 | 37.83 | −107.70 (0.50) |
| Protein-ligand | |||||||
| PDE6δ-D14 | −47.22 (0.15) | − 120.27 (0.95) | 134.17 (0.86) | − 6.40 (0.02) | −53.62 | 13.90 | −39.72 (0.20) |
| PDE6δ-C22 | −41.76 (0.15) | −173.27 (0.47) | 163.16 (0.38) | −6.54 (0.01) | −48.30 | −10.11 | − 58.41 (0.19) |
Binding free energies and individual energy terms of complexes starting from docked conformations (kcal/mol). The polar (ΔEpolar = ΔEele + ΔGele,sol) and non-polar (ΔEnon-polar = ΔEvwd + ΔGnpol,sol) contributions are shown. All the energies are averaged over 500 snapshots at time intervals of 100 ps from the last 50 ns-long MD simulations and are in kcal/mol (± standard error of the mean)