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

## TL;DR

This study uses computational and experimental methods to understand how endocrine-disrupting chemicals bind to hormone receptors, helping identify key molecular events.

## Contribution

The study combines molecular simulations and experiments to validate binding patterns of EDCs to estrogen and androgen receptors.

## Key findings

- MM-GBSA and RBFE calculations confirmed experimental trends in bisphenol compound binding affinity.
- Common binding patterns were identified, offering a framework for future EDC research.
- Agreement between computational and experimental methods supports their combined use in EDC studies.

## Abstract

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, in silico 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.