Table 5. Changes in System Energy Following Compound Docking and Molecular Dynamicsa.
| model | compound | delta energy (kJ/mol) | delta VdM (kJ/mol) | delta Coulomb (kJ/mol) |
|---|---|---|---|---|
| 1FUU | 167 | –183.96 | –75.15 | –44.69 |
| 1FUU | 162 | –173.49 | –88.03 | –61.9 |
| 1FUU | 157 | –113.39 | –20.4 | –68.4 |
| 1FUU | 139 | –5.52 | –41.22 | –21.91 |
| 1FUU | 127 | –71.86 | –16.29 | –26.7 |
a
Prime MMGBSA was used to calculate the change in total energy, vDw energy, and Coulombic energy at the beginning (open conformation) and end of molecular dynamic simulations (closed conformation). In all top compounds identified in the virtual screen and biochemical screen, there is a marked reduction in overall energy in the system representative of favorable ligand–protein interactions and interdomain interactions reflected in the promotion of stabilization of the protein in the closed conformation. The most potent compound, UM167, demonstrates the greatest reduction of total energy upon binding the 1FUU model.