Table 2.

Relative binding free energies $\mathrm{\Delta }\mathrm{\Delta }G=\mathrm{\Delta }{G}_{\mathit{binding}}^{\mathit{mut}}-\mathrm{\Delta }{G}_{\mathit{binding}}^{\mathit{WT}}$ for six ligands with two ER mutations—L384V and L387R—from ESMACS and TIES approaches.

Ligand	∆∆GESMACS		∆∆GTIES		pdb
	L384V	L387R	L384V	L387R
4-OHT	1.3 ± 1.1	1.0 ± 1.3	2.2 ± 0.4	5.1 ± 0.5	3ert
EDO	0.3 ± 1.1	0.9 ± 1.3	2.0 ± 0.4	4. 8 ± 0.5	3ert
RAL	3.9 ± 1.9	3.6 ± 2.0	2.2 ± 0.4	6.1 ± 0.9	3ert
TMX	0.6 ± 1.0	3.4 ± 1.2	2.2 ± 0.4	4.7 ± 0.6	3ert
TOR	0.2 ± 1.0	4.3 ± 1.3	2.2 ± 0.5	4.6 ± 0.6	3ert
E2	1.7 ± 1.2	1.3 ± 1.3	2.2 ± 0.3	5.2 ± 1.8	1qku

Control E2	L387A	Y537S	D538G	pdb
∆∆GESMACS	3.9 ± 1.3	1.0 ± 0.9	1.0 ± 0.9	1qku
∆∆GTIES	1.8 ± 0.2	− 0.4 ± 0.5	− 0.5 ± 0.6	1qku
∆∆Gexp	0.5 ± 0.210	1.1 ± 0.438	1.2 ± 0.438	–

The calculations for the three mutations taken from the literature—L387A, Y537S and D538G—are presented as a control. The Poisson-Boltzmann (PB) free energy methods were used in the predictions of the ESMACS free energies, while alchemical approach was used for TIES. All energy values are in kcal/mol.