Table 2 Relative binding free energies \(\Delta \Delta G~ = ~\Delta G_{{binding}}^{{mut}} - \Delta G_{{binding}}^{{WT}}\) for six ligands with two ER mutations—L384V and L387R—from ESMACS and TIES approaches.

From: The effect of protein mutations on drug binding suggests ensuing personalised drug selection

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

–

 
  1. 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.
Back to article page