Assessment of the Binding Patterns for Endocrine Disrupting Chemicals in Complex with Estrogen and Androgen Receptors by Leveraging the Asclepios Enalos KNIME Nodes

Endocrine disrupting chemicals (EDCs) have been shown to mediate metabolic disruptions in human cells and have been associated with severe adverse health effects. By antagonizing the hormones that act on nuclear hormone receptors, like the estrogen receptor α (ERα) and the androgen receptor (AR), these chemicals disrupt the regulation of various biochemical processes, thereby adversely affecting metabolic homeostasis. The expression of estrogen and androgen receptors in the liver and pancreas, which play an important role in lipid and glucose homeostasis regulation, has made them prime targets affected by EDCs. The different chemical structures of EDCs impose limitations on elucidating their binding mechanisms in nuclear receptors. In this context, <i>in silico</i> tools are able to highlight the potential interactions between the chemicals and the receptors. The aim of this study is to apply molecular simulation and experimental techniques to identify common patterns in the binding process of selected EDCs to ERα and AR and, thus, pinpoint key elements that could be characterized as molecular initiating events (MIE). MM-GBSA and alchemical relative binding free energy (RBFE) calculations have verified the trends observed in the experimental assays regarding the binding affinity of bisphenol compounds. The findings that confirm the agreement between computational and experimental methods offer a framework for future studies on the behavior of EDCs with other metabolically relevant receptors.