Table 3 The calculated and experimental changes in binding free energies of 8 sNRIs-hNET complexes (2 sNRIs against 4 single-point mutations) before and after those mutations in hNET25 (ΔG is in kcal/mol).
sNRIs studied | Single point mutations in hNET | Calculated value | Experimental value25 | ||
|---|---|---|---|---|---|
ΔΔGcalca | Fold-change of potency b | Fold-change of potency c | ΔΔGexpd | ||
Atomoxetine | F72Y | −0.03 | 0.95 | 0.78 (0.55~1.14) | −0.15 (−0.35~0.08) |
N153S | −0.31 | 0.59 | 2.33 (1.73~3.29) | 0.50 (0.33~0.71) | |
F323Y | 1.93 | 25.95 | 3.89 (2.45~6.14) | 0.81 (0.53~1.08) | |
S419T | 1.27 | 8.52 | 12.67 (8.73~18.86) | 1.51 (1.28~1.74) | |
Maprotiline | F72Y | −0.31 | 0.59 | 0.59 (0.34~0.99) | −0.31 (−0.64~−0.01) |
N153S | 0.05 | 1.09 | 2.34 (1.44~3.75) | 0.50 (0.22~0.78) | |
F323Y | 0.96 | 5.05 | 4.97 (3.21~7,75) | 0.95 (0.69~1.21) | |
S419T | 1.36 | 9.92 | 5.88 (3.61~9.43) | 1.05 (0.76~1.33) | |
- Detail information of each energy term can be found in SI, Table S4.
- aΔΔGcalc = Gmutation − ΔGwild type.
- bFold-changes of potency were derived from ΔΔGcalc by the equation ΔΔGcalc = RTln (FCpotency).
- cFold-changes of potency measured by Ki values
25. Numbers out of the bracket indicated the fold-changes derived from the medium experimental values of both 
and 
. The first number in the bracket indicated the minimum fold-changes, while the second one indicated the maximum fold-changes. - dΔΔGexp were derived from the FCpotency by the equation ΔΔGexp = RTln (FCpontency).
and 
. The first number in the bracket indicated the minimum fold-changes, while the second one indicated the maximum fold-changes.