FMO Study of the Interaction Energy between Human Estrogen Receptor $\alpha$ and Selected Ligands

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.Comment: 15 pages, 9 figures. arXiv admin note: text overlap with arXiv:2012.1082