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The Role Of Ligand Flexibility In Predicting Biological Activity: Structure–Activity Relationships For Aryl Hydrocarbon, Estrogen, And Androgen Receptor Binding Affinity, Steven P. Bradbury, Ovanes G. Mekenyan, Gerald T. Ankley

Steven P. Bradbury

Recent studies indicate that the potency and agonist or antagonist activity of steroid hormone ligands are dependent, in part, on ligand–receptor binding affinity as well as the conformation of the ligand–receptor complex. The binding of ligands to hormone receptors is thought to involve interactions by which shapes of both the receptor and ligand are modified in the formation of the ligand–receptor complex. As a consequence, it is essential to explore the significance of ligand flexibility in the development of screening-level structure–activity relationships. In this review, examples are provided of techniques used to generate and screen ligand conformers in the development …