  Fragment molecular orbital (FMO) calculations were performed in aqueous media
which allowed us to obtain the interaction energy between the human estrogen
receptor $\alpha$ ligand-binding domain (ER) and the selected ligands (L):
17$\beta$-estradiol (E2), 17$\alpha$-estradiol (17$\alpha$-E2), estriol (E3),
genistein (GNT), diethylstilbestrol (DES), bisphenol A (BPA), bisphenol AF
(BPAF), hydroxychlor (HPTE) and methoxychlor (DMDT). These calculations were
carried out on representative structures of L-ER complexes obtained from
molecular dynamics simulations. The MP2/6-31G(d) L-ER FMO interaction energy in
kcal/mol is as follows:
  E3 (-100.1) < GNT (-95.8) < E2 (-88.5) < BPA (-84.7) < DES (-82.6) < BPAF
(-80.6) < 17$\alpha$-E2 (-78.7) < HPTE (-75.9) < DMDT (-46.3)
  The central hydrophobic core of the ligands interacts attractively with
several apolar amino acid residues of ER. Glu 353 and His 524 interacts
strongly with most ligands through a hydrogen bond with the hydroxyl group of
the phenol A-ring and the terminal hydroxylated ring, respectively. Water
molecules were found at the binding site of receptor. In our model systems we
have demonstrated what is generally observed in ligand-receptor complexes: the
steric and chemical complementarity of the groups on the ligand and binding
site surfaces.
