A MOLECULAR MODELING ANALYSIS OF DIETHYLSTILBESTROL CONFORMATIONS ANDTHEIR SIMILARITY TO ESTRADIOL-17-BETA

Crystallographic and computer modeling studies throughout the last 25 years have shown the structure of diethylstilbestrol (DES) to exist in two symmetrical or one asymmetrical conformation. As a result of spec ific comparisons to estradiol-17 beta (E(2)), the asymmetrical DES con former has been suggested as the geometry possessing estrogenic activi ty. In the present study, a more complete set of DES conformations has been elucidated through the use of computer modeling. All previously defined DES geometries were found within this new set of ten structura l forms. Differences between the molecular mechanics heat of formation energies of the ten conformers, as well as the transition energies se parating them from each other, were found to be less than I kcal/mol. Additionally, a computer-based molecular alignment method was employed to quantitatively compare the steric and electrostatic molecular feat ures of each DES conformer relative to E(2). All ten DES structures we re found to have shape relationships similar to E(2). Thus, a model fo r the estrogen action of DES is presented whereby this stilbene can fa vorably interact with the estrogen receptor regardless of the conforma tion or orientation of the initial ligand-receptor association.