Computational Approaches to Identify a Novel Binding Site on Estrogen Receptor α

Abstract

3,3‐bis(4‐hydroxyphenyl)‐7‐methyl‐1,3,dihydro‐2H‐indol‐2‐one (BHPI) is a biomodulator of Estrogen Receptor alpha (ERα) that targets ERα positive cancer cells by activating the unfolded protein response (UPR). BHPI induces strong and sustained activation of this pathway, eventually leading to necrotic cell death. While much is known about how BHPI triggers the UPR leading to necrotic cell death, it is not known how BHPI binds to its putative molecular target, ERα. In an effort to identify the binding site of BHPI on ERα, molecular docking studies in AutoDock Vina were utilized. This work uncovered a novel binding site that is not targeted by classical ligands, such as estrogen and tamoxifen.