# A Computational Framework to Evaluate Interactions of BPA and Its Analogs with Human Liver X Receptor-Beta for Health Risk Assessment

## TL;DR

This study uses computer models to show that BPA alternatives may be more harmful to liver health than BPA itself.

## Contribution

A novel computational framework is introduced to assess the hepatotoxic potential of BPA analogs via LXRβ interactions.

## Key findings

- Several BPA analogs showed stronger binding to LXRβ than BPA.
- Some analogs have similar pharmacokinetic profiles to BPA but stronger LXRβ interactions.
- The study highlights the hepatotoxic risk of BPA alternatives using in silico methods.

## Abstract

Bisphenols are widely used in industrial applications
to produce
plastics and other consumer products. Among them, bisphenol A (BPA)
is the most extensively studied due to its well-documented endocrine-disrupting
effects and its association with various health conditions, including
metabolic disorders and liver disease. Due to its known toxicity,
BPA use has been restricted in many countries, leading to the emergence
of several structural analogs. Recent studies have shown that BPA
can interfere with normal liver metabolism by interacting with Liver
X Receptor-beta (LXRβ). Although some BPA analogs have also
been reported to cause toxicity, their exact effects on LXRβ
remain unclear. In this study, we investigated the interaction between
BPA analogs and LXRβ using molecular docking. BPA and the known
LXRβ ligand G58 were used as reference compounds. The top 10
BPA analogs were further evaluated for their pharmacokinetics and
pharmacodynamics properties. Molecular dynamics simulations over 100
ns were performed to study the dynamic behavior of LXRβ in complex
with these analogs. Binding free energies were then calculated using
the MM-PBSA method. Our results showed that several BPA analogs exhibited
predicted stronger binding activities to LXRβ than BPA. Although
some analogs shared similar pharmacokinetic and pharmacodynamic profiles
with BPA, their stronger interaction with LXRβ raises concerns
about their potential hepatotoxicity. This study employs a robust in silico framework to predict that commonly used BPA alternatives
may pose a greater potential hepatotoxic risk than the banned parent
compound, highlighting the value of computational approaches in prioritizing
chemicals for further experimental assessment.