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

TL;DR

This study uses fragment molecular orbital calculations to analyze the interaction energies between human estrogen receptor alpha and various ligands, revealing key binding interactions and energetic rankings.

Contribution

It applies FMO calculations to ligand-receptor complexes derived from molecular dynamics, providing detailed interaction energy insights for multiple ligands.

Findings

E3 has the strongest interaction energy with ER

Hydrogen bonds with Glu 353 and His 524 are significant

Water molecules are present at the binding site

Abstract

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.