Table 2.

Ligand-surrounding energies and calculated binding free energies from the MD simulation resulting in the lowest binding free energy for each ligand

	${\langle V_{\text{l}-\text{s}}^{\text{vdW}}\rangle }_{\text{f}}$	${\langle V_{\text{l}-\text{s}}^{\text{vdW}}\rangle }_{\text{b}}$	${\langle V_{\text{l}-\text{s}}^{\text{el}}\rangle }_{\text{f}}$	${\langle V_{\text{l}-\text{s}}^{\text{el}}\rangle }_{\text{b}}$	$\Delta G_{\text{LIE}}^{\text{bind}}$	$\Delta G_{\text{obs}}^{\text{bind}}$ (31)
7b	−38.4 ± 0.3	−67.3 ± 0.4	−78.5 ± 1.5	−70.4 ± 1.2	−5.2 ± 1.3	−6.9
7c	−34.8 ± 0.2	−62.7 ± 0.1	−73.6 ± 1.7	−68.0 ± 0.1	−6.1 ± 0.8	−6.8
15a	−35.5 ± 0.2	−53.6 ± 0.4	−27.6 ± 0.5	−31.1 ± 0.8	−8.2 ± 0.6	−7.5
17a	−38.5 ± 0.3	−60.8 ± 1.2	−32.3 ± 0.9	−36.6 ± 0.6	−9.4 ± 0.9	−8.4
17c	−40.0 ± 0.3	−65.0 ± 0.0	−38.7 ± 0.7	−39.9 ± 0.4	−8.5 ± 0.5	−8.4
17f	−38.9 ± 0.3	−66.4 ± 0.2	−24.5 ± 0.9	−22.4 ± 0.2	−7.5 ± 0.5	N/A*
17g	−36.7 ± 0.2	−61.7 ± 0.7	−28.7 ± 0.3	−29.3 ± 0.5	−8.3 ± 0.5	−7.5
17o	−42.4 ± 0.4	−69.9 ± 0.4	−40.7 ± 0.8	−42.8 ± 0.2	−9.3 ± 0.5	−9.3

All values are in kcal/mol. ${\langle \rangle }_{\text{f}}$ and ${\langle \rangle }_{\text{b}}$ denote interaction energy averages for the free and bound states of the ligand, respectively. Errors are calculated as half of the difference between the averages of the first and second half of the data collection trajectory. Observed binding free energies are derived from $\Delta G_{\text{obs}}^{\text{bind}}\simeq RT\text{ln}I{C}_{50}$, with a 1 M standard state. A γ-value of −3.47, obtained from a least-square fitting of the calculated binding free energies (not including 17f) to $\Delta G_{\text{obs}}^{\text{bind}}$, was used to calculate $\Delta G_{\text{LIE}}^{\text{bind}}$.

^*No IC₅₀-value is available for compound 17f in Peukert et al. (31); see also Table 1.