Molecular simulation of interaction between estrogen receptor and selective estrogen receptor modulators

To study the mechanism of interaction between a series of potent racemic selective estrogen receptor modulators (SERM) and estrogen receptors (ER).

Active conformations of these conformationally restricted raloxifene analogues in binding pocket were determined by molecular mechanics. The interactive energies between ligand and receptor were calculated by docking program.

Both R and S configurations of these SERM were accommodated by the binding pocket of ER. The hydroxy group of compounds forms hydrogen bonds with amino acid residues of ER and the phenolic group mimics the A ring of estradiol. The most potential compounds were those with two hydroxy groups and accommodated by binding pocket in S configuration with phenolic group at C(16) imitating A ring of estradiol.

Chiral center conferred little effect on the binding affinity of these conformationally restricted raloxifene analogues. The hydroxy group(s) play(s) a critical role to the orientation of compounds in active pocket of ER and the binding between ligand and receptor.