Determining the Theoretical Binding Site of BHPI on Estrogen Receptor Alpha Using Computational Methods

Abstract

BHPI is a non-competitive biomodulator that targets estrogen receptor alpha (ERα) positive cancers. This small molecule drug activates the anticipatory unfolded protein response (aUPR), and has been shown to effectively eliminate drug-resistant breast and ovarian cancers as a monotherapy and in combination. By triggering a strong and sustained aUPR, ATP is depleted in cancer cells, leading to eventual necrotic cell death. The binding site of BHPI on ERα is currently unknown. Through the use of computational tools such as PyMOL, RefineD, and SwissDock, we sought to determine the putative binding site of BHPI on three different ERα PDBs: 3ert, 1a52, and 5u2b. This work will allow deeper understanding of BHPI, its mechanism-of-action, and possibly, how it triggers the aUPR.