Table 1. Comparison of experimental ΔΔG in oseltamivir and zanamivir for three NA mutations with estimates obtained using different computational approaches.
| Method | H274Y | N294S | Y252H | RMSE | |||
| ΔΔG, kcal/mol | ΔΔG, kcal/mol | ΔΔG, kcal/mol | (RMSD), kcal/mol | ||||
| zanamivir | oseltamivir | zanamivir | oseltamivir | zanamivir | oseltamivir | ||
| Experimentala | 0.4 (0.1) | 3.3 (0.2) * | 1.2 (0.1) * | 2.6 (0.2) * | 0.1 (0.2) | −1.4 (0.1) | N/A (0.2) |
| SRMM | −5.8 (7.4) | 0.7 (7.0) | 8.2 (7.7) | 5.8 (6.2) | −0.1 (8.7) | −0.9 (7.4) | 4.2 (7.4) |
| SRSM | 1.7 (2.9) | 1.2 (3.0) | 0.6 (2.0) | 1.7 (1.9) | 1.5 (1.7) | 0.5 (1.5) | 1.5 (2.2) |
| SRSM/HREX | 1.3 (0.8) | 4.1 (2.4) | 2.3 (0.4) | 2.2 (0.9) | 0.6 (0.8) | 0.7 (1.4) | 1.1 (1.1) |
| MM-GBSA | 6.2 (8.1) | 0.9 (3.8) | 5.7 (6.1) | −5.9 (3.6) | 2.1 (2.9) | −1.9 (3.0) | 4.8 (4.6) |
| MM-PBSA | 8.4 (10.1) | 3.0 (3.9) | 5.8 (4.5) | −4.7 (3.2) | 2.8 (3.1) | 0.2 (2.6) | 5.0 (4.6) |
| Rosetta | −0.4 (0.5) | 0.8 (0.4) | −0.4 (0.3) | 0.3 (0.2) | −0.1 (0.4) | 0.0 (0.0) | 1.7 (0.3) |
a
Values were derived from the data reported by Collins et al [10].
Standard deviations are shown in parentheses. Root mean squared error (RMSE) and the RMS Standard Deviation (RMSD) are provided.
‘*’
indicates experimentally determined drug resistant mutation. ‘N/A’ stands for not applicable.