A computational insight into endocrine disruption by polychlorinated biphenyls via non-covalent interactions with human nuclear receptors

Production of polychlorinated biphenyls (PCBs) was banned a long time ago because of their harmful health effects but humans continue to be exposed to residual PCBs in the environment. In this study, the susceptibility of human nuclear receptors to binding by PCBs was investigated using molecular docking simulation. Findings revealed that PCBs belonging to ortho-substituted, mono-ortho-substituted and non-ortho-substituted congeners could bind to agonistic conformations of androgen (AR), estrogen (ER ? and ER 13), glucocorticoid (GR) and thyroid hormone (TR ? and TR 13) receptors as well as antagonistic conformation of androgen receptor (AR an) but only ortho-substituted and mono-ortho-substituted PCBs could bind to estrogen receptors in their antagonistic conformations (ER ? an and ER 13 an). Further molecular docking analyses showed that PCBs mimic the modes of interaction observed for the co-crystallized ligands in the crystal structures of the affected receptors, utilizing 81%, 83%, 78%, 60%, 75%, 60%, 86%, 100% and 75% of the amino acid residues utilized by the co-crystallized ligands for binding in AR, AR an, ER ?, ER ? an, ER 13, ER 13 an, GR, TR ? and TR 13 respectively. This computational study suggests that PCBs may cause endocrine disruption via formation of non-covalent interactions with androgen, estrogen, glucocorticoid and thyroid hormone receptors.

Automated summary

The research suggests that polychlorinated biphenyls (PCBs) may disrupt the endocrine system by forming non-covalent interactions with androgen, estrogen, glucocorticoid, and thyroid hormone receptors.