  Estrogen receptors (ERs) are a group of proteins activated by
17$\beta$-estradiol. The endocrine-disrupting chemicals (EDCs) mimic estrogen
action by bind directly to the ligand binding domain of ER. From this
perspective, ER represent a good model for identifying and assessing the health
risk of potential EDCs. This ability is best reflected by the ligand-ER binding
energy. Multilayer fragment molecular orbital (MFMO) calculations were
performed which allowed us to obtain the binding energy using a calculation
scheme that considers the molecular interactions that occur on the following
model systems: the bound and free receptor, 17$\beta$-estradiol and a water
cluster. The bound and free receptor and 17$\beta$-estradiol were surrounded by
a water shell containing the same number of molecules as the water cluster. The
structures required for MFMO calculations were obtained from molecular dynamics
simulations and cluster analysis. Attractive dispersion interactions were
observed between 17$\beta$-estradiol and the binding site hydrophobic residues.
In addition, strong electrostatic interactions were found between
17$\beta$-estradiol and the following charged/polarized residues: Glu 353, His
524 and Arg 394. The FMO2-RHF/STO-3G:MP2/6-31G(d) weighted binding energy was
of -67.2 kcal/mol. We hope that the model developed in this study can be useful
for identifying and assessing the health risk of potential EDCs.
