Structures of Endocrine-Disrupting Chemicals Determine Binding to and Activation of the Estrogen Receptor α and Androgen Receptor

What is it about?

Endocrine-disrupting chemicals (EDCs) can interact with nuclear receptors, including estrogen receptor α (ERα) and androgen receptor (AR), to affect the normal endocrine system function, causing severe symptoms. Here, we employed a series of computational methodologies to investigate the structural features of EDCs that bind to and activate ERα and AR based on more than 4000 compounds. We used molecular docking and molecular dynamics simulations to elucidate the functional consequences and validated structure−function correlations experimentally. We found that EDCs share three levels of key fragments. Primary and secondary fragments are responsible for the binding to receptors, and tertiary fragments determine the activity type (agonist, antagonist, or mixed). Discovering the three levels of key fragments may drive fast screening and evaluation of potential EDCs from large sets of compounds.

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Photo by Ayush Kumar on Unsplash

Photo by Ayush Kumar on Unsplash