Table 2.
Virtual screening of bacterial compounds against M. tuberculosis macromolecular targets (PknG and Pks13).
| Complex | Mol MW (170–725) | Dipole (1.0–12.5) | SASA | *QplogS (− 6.5 to 0.5) | PSA (7.0–200.0) | Volume | %Human oral absorption | XP GScorea (kcal/mol) | XP Gscoreb | Pre-MD-MM-GBSAa ΔGbind (kcal/mol) | Pre-MD-MM-GBSAb ΔGbind (kcal/mol) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| PknG-ligand complex | |||||||||||
| Maculosin | 260.29 | 2.96 | 528.57 | − 1.09 | 92.29 | 875.01 | 59.48 | − 9.4 | − 9.4 | − 35.7 | − 35.7 |
| NPA006809 | 234.26 | 3.85 | 466.23 | − 2.38 | 103.50 | 775.73 | 71.17 | − 9.4 | − 9.4 | − 39.8 | − 39.8 |
| 5′-Deoxytoyocamycin | 275.27 | 6.02 | 487.25 | − 3.16 | 128.19 | 829.80 | 54.70 | − 9.3 | − 9.3 | − 38.0 | − 38.2 |
| (3R,8aR)-3-benzyl-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione | 244.29 | 1.80 | 516.11 | − 1.20 | 69.75 | 852.12 | 72.70 | − 9.1 | − 9.0 | − 41.1 | − 41.0 |
| Cyclo(Pro-Leu) | 210.28 | 1.90 | 458.39 | − 0.05 | 69.87 | 764.78 | 68.98 | − 8.9 | − 8.9 | − 42.6 | − 42.6 |
| Cyclo-(L-Pro-4-OH-L-Leu) | 226.28 | 3.50 | 473.85 | − 0.50 | 88.06 | 789.50 | 64.63 | − 8.8 | − 8.8 | − 42.8 | − 42.8 |
| Cyclo(2-hydroxy-Pro-R-Leu) | 226.26 | 2.14 | 330.80 | 0.11 | 87.68 | 781.66 | 61.59 | − 8.8 | − 8.5 | − 34.7 | − 35.1 |
| Control (8ZC) | − 9.5 | − 9.5 | − 48.4 | − 48.4 | |||||||
| Pks13-ligand complex | |||||||||||
| Vazabitide A | 271.32 | 13.40 | 515.62 | − 0.90 | 133.66 | 27.76 | − 11.9 | − 8.218 | − 47.6 | − 47.6 | |
| Control (7IJ) | − 8.2 | − 8.2 | − 42.0 | − 42.0 | |||||||
aLigands docked using OPLS4 force field.
bLigands docked after M06-2X/6-311++ G(d,p) optimization. SASA (solvent accessible surface area). MW (molecular weight).