Table 1.

Binding free energies and individual energy terms of inhibitors in complex with TPH1 (kcal/mol).

Contribution	1a	1b	1c	1d
$\mathrm{\Delta }{\text{E}}_{\text{int}}^{ele}$	−49.8 (0.82)	−45.7 (0.82)	−47.3 (0.85)	−52.5 (0.55)
$\mathrm{\Delta }{\text{E}}_{\text{int}}^{vdw}$	−42.8 (0.25)	−41.7 (0.45)	−49.3 (0.39)	−41.0 (0.37)
$\mathrm{\Delta }{\text{G}}_{sol}^{nopol}$	−6.0 (0.02)	−7.677 (0.02)	−6.9 (0.03)	−6.6 (0.04)
$\mathrm{\Delta }{\text{G}}_{sol}^{ele}$	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

^aThe polar/nonpolar ( $\mathrm{\Delta }{\text{G}}_{sol}^{ele}+\mathrm{\Delta }{\text{G}}_{sol}^{nopol}$) contributions;

^bThe electrostatic ( $\mathrm{\Delta }{\text{E}}_{\text{int}}^{ele}+\mathrm{\Delta }{\text{G}}_{sol}^{ele}$) contributions. All energies are averaged over 150 snapshots and are given in kcal/mol. Calculation of ΔG_bind does not explicitly consider entropy contributions. The values in parentheses represent the standard error of the mean;

^cExperimental binding free energies are calculated from IC₅₀ using the following relationship: ΔG_bind = RTlnK_dissociated = RTln (IC₅₀ + 0.5C_enzyme) ≈ RTlnIC₅₀, where R is ideal gas constant, T is temperature in K (298 K is used in this article), and C_enzyme is the concentration of enzyme, which is a very small number after equilibration and can be omitted in most cases.