# QSTR Models in Dioxins and Dioxin-like Compounds Provide Insights into Gene Expression Dysregulation

## TL;DR

This study explores how dioxin-like compounds affect gene expression by analyzing their molecular structures and interactions with biological receptors.

## Contribution

The study introduces strong QSTR models and molecular docking simulations to explain how dioxin-like compounds interfere with gene regulation.

## Key findings

- QSTR models with r2 > 0.95 and p < 0.0001 link molecular structures of PCDD/Fs to toxicity endpoints.
- PCDD/Fs show comparable or better binding affinities to nuclear receptors than natural ligands.
- Molecular dynamics simulations reveal how PCDD/Fs may disrupt transcription and gene expression.

## Abstract

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) are a group of organic chemicals containing three-ring structures that can be substituted with one to eight chlorine atoms, leading to 75 dioxin and 135 furan congeners. As endocrine-disrupting chemicals (EDCs), they can alter physiological processes causing a number of disorders. In this study, quantitative structure–toxicity relationship (QSTR) studies were used to determine the correlations between the PCDD/Fs’ molecular structures and various toxicity endpoints. Strong QSTR models, with the coefficients of determination (r2) values greater than 0.95 and ANOVA p-values less than 0.0001 were established between molecular descriptors and the endpoints of bioconcentration, fathead minnow LC50, and Daphnia magna LC50. The ability of PCDD/Fs to bind to several nuclear receptors was investigated via molecular docking studies. The results show comparable, and in some instances better, binding affinities of PCDD/Fs toward the receptors relative to their natural agonistic and antagonistic ligands, signifying possible interference with the receptors’ natural biological activities. These studies were accompanied by the molecular dynamics simulations of the top-binding PCDD/Fs to show changes in the receptor–ligand complexes during binding and provide insights into these compounds’ ability to interfere with transcription and thereby modify gene expression. This introspection of PCDD/Fs at the molecular level provides a deeper understanding of these compounds’ toxicity and opens avenues for future studies.