Table 1.
Contribution | 1a | 1b | 1c | 1d |
---|---|---|---|---|
−49.8 (0.82) | −45.7 (0.82) | −47.3 (0.85) | −52.5 (0.55) | |
−42.8 (0.25) | −41.7 (0.45) | −49.3 (0.39) | −41.0 (0.37) | |
−6.0 (0.02) | −7.677 (0.02) | −6.9 (0.03) | −6.6 (0.04) | |
66.9 (0.59) | 68.837 (0.52) | 69.2 (0.86) | 66.7 (0.67) | |
ΔGsola | 60.9(0.58) | 61.2 (0.51) | 62.3 (0.84) | 60.1 (0.59) |
ΔGeleb | 17.1 (0.38) | 23.1 (0.53) | 21.9 (0.58) | 14.2 (0.43) |
−TΔS | −12.6 | −11.8 | −13.3 | −13.0 |
ΔG bind | −46.2 (0.41) | −38.0 (0.39) | −47.6 (0.56) | −46.4 (0.33) |
IC50(nM) | 32 | 380 | 26 | 44 |
ΔGexpc | −42.7 | −36.6 | −43.3 | −42.0 |
The polar/nonpolar ( ) contributions;
The electrostatic ( ) contributions. All energies are averaged over 150 snapshots and are given in kcal/mol. Calculation of ΔGbind does not explicitly consider entropy contributions. The values in parentheses represent the standard error of the mean;
Experimental binding free energies are calculated from IC50 using the following relationship: ΔGbind = RTlnKdissociated = RTln (IC50 + 0.5Cenzyme) ≈ RTlnIC50, where R is ideal gas constant, T is temperature in K (298 K is used in this article), and Cenzyme is the concentration of enzyme, which is a very small number after equilibration and can be omitted in most cases.