Table 3. Data from MD Simulations for Compounds 4, 4a, 4b, 5, and 5aa.
| 4 | 4a | 4b | 5 | 5a | |
|---|---|---|---|---|---|
| Molecular Mechanics/Poisson–Boltzmann Surface Area | |||||
| ΔGbind kcal mol–1 (±SD) | –78.5 (±4.4) | –72.4 (±4.4) | –70.0 (±4.0) | –87.7 (±5.0) | –84.2 (±4.6) |
| Hydrogen Bonding | |||||
| <NHB> | 1.806 | 1.861 | 1.413 | 1.731 | 0.861 |
| ΔGHB (kJ mol–1) | –20.8 | –24.8 | –25.1 | –21.7 | –20.1 |
| τ (ps) | 490 | 2363 | 2613 | 700 | 377 |
| Protein–Ligand Interactions | |||||
| ligand efficiency | 0.29 (7/23) | 0.30 (6/20) | 0.08 (2/23) | 0.27 (6/22) | 0.29 (5/17) |
| CIc | 0.71 | 0.66 | 0.55 | 0.95 | 0.92 |
| Oil–Water Partition Coefficient | |||||
| molinspiration log P | 8.91 | 6.72 | 6.38 | 5.45 | 5.79 |
a
ΔGbind, relative free-energy of binding; ΔGHB, hydrogen-bond formation energy; <NHB>, average number of hydrogen-bonds per time frame; τ, hydrogen bond lifetime; CIc, cross-interactions capability; logP, octanol–water partition coefficient.