In silico prediction of nuclear receptor binding to polychlorinated dibenzofurans and its implication on endocrine disruption in humans and wildlife
Polychlorinated dibenzofurans (PCDFs) are known to cause endocrine disruption in humans and wildlife but the mechanisms underlying this disruption have not been adequately investigated. In this paper, the susceptibility of the endocrine system to disruption by PCDF congeners via nuclear receptor bin...
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doaj-66eccba4cddf47b597144c5abf4bf7682021-10-11T04:16:48ZengElsevierCurrent Research in Toxicology2666-027X2021-01-012357365In silico prediction of nuclear receptor binding to polychlorinated dibenzofurans and its implication on endocrine disruption in humans and wildlifeLukman K. Akinola0Adamu Uzairu1Gideon A. Shallangwa2Stephen E. Abechi3Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria; Department of Chemistry, Bauchi State University, Gadau, Nigeria; Corresponding author at: Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria.Department of Chemistry, Ahmadu Bello University, Zaria, NigeriaDepartment of Chemistry, Ahmadu Bello University, Zaria, NigeriaDepartment of Chemistry, Ahmadu Bello University, Zaria, NigeriaPolychlorinated dibenzofurans (PCDFs) are known to cause endocrine disruption in humans and wildlife but the mechanisms underlying this disruption have not been adequately investigated. In this paper, the susceptibility of the endocrine system to disruption by PCDF congeners via nuclear receptor binding was studied using molecular docking simulation. Findings revealed that some PCDF congeners exhibit high probabilities of binding to androgen receptor in its agonistic and antagonistic conformations. In depth molecular docking analysis of the receptor-ligand complexes formed by PCDFs with androgen receptor in its agonistic and antagonistic conformations showed that, these complexes were stabilized by electrostatic, van der Waals, pi-effect and hydrophobic interactions. It was also observed that PCDF molecules mimic the modes of interaction observed in androgen-testosterone and androgen-bicalutamide complexes, utilizing between 65 and 83% of the amino acid residues used by the co-crystallized ligands for binding. This computational study suggests that some PCDF congeners may act as agonists and antagonists of androgen receptor in humans and wildlife via inapproprate binding to the receptor.http://www.sciencedirect.com/science/article/pii/S2666027X21000347Endocrine disruptionMolecular dockingNon-covalent interactionNuclear receptorPolychlorinated dibenzofurans |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lukman K. Akinola Adamu Uzairu Gideon A. Shallangwa Stephen E. Abechi |
spellingShingle |
Lukman K. Akinola Adamu Uzairu Gideon A. Shallangwa Stephen E. Abechi In silico prediction of nuclear receptor binding to polychlorinated dibenzofurans and its implication on endocrine disruption in humans and wildlife Current Research in Toxicology Endocrine disruption Molecular docking Non-covalent interaction Nuclear receptor Polychlorinated dibenzofurans |
author_facet |
Lukman K. Akinola Adamu Uzairu Gideon A. Shallangwa Stephen E. Abechi |
author_sort |
Lukman K. Akinola |
title |
In silico prediction of nuclear receptor binding to polychlorinated dibenzofurans and its implication on endocrine disruption in humans and wildlife |
title_short |
In silico prediction of nuclear receptor binding to polychlorinated dibenzofurans and its implication on endocrine disruption in humans and wildlife |
title_full |
In silico prediction of nuclear receptor binding to polychlorinated dibenzofurans and its implication on endocrine disruption in humans and wildlife |
title_fullStr |
In silico prediction of nuclear receptor binding to polychlorinated dibenzofurans and its implication on endocrine disruption in humans and wildlife |
title_full_unstemmed |
In silico prediction of nuclear receptor binding to polychlorinated dibenzofurans and its implication on endocrine disruption in humans and wildlife |
title_sort |
in silico prediction of nuclear receptor binding to polychlorinated dibenzofurans and its implication on endocrine disruption in humans and wildlife |
publisher |
Elsevier |
series |
Current Research in Toxicology |
issn |
2666-027X |
publishDate |
2021-01-01 |
description |
Polychlorinated dibenzofurans (PCDFs) are known to cause endocrine disruption in humans and wildlife but the mechanisms underlying this disruption have not been adequately investigated. In this paper, the susceptibility of the endocrine system to disruption by PCDF congeners via nuclear receptor binding was studied using molecular docking simulation. Findings revealed that some PCDF congeners exhibit high probabilities of binding to androgen receptor in its agonistic and antagonistic conformations. In depth molecular docking analysis of the receptor-ligand complexes formed by PCDFs with androgen receptor in its agonistic and antagonistic conformations showed that, these complexes were stabilized by electrostatic, van der Waals, pi-effect and hydrophobic interactions. It was also observed that PCDF molecules mimic the modes of interaction observed in androgen-testosterone and androgen-bicalutamide complexes, utilizing between 65 and 83% of the amino acid residues used by the co-crystallized ligands for binding. This computational study suggests that some PCDF congeners may act as agonists and antagonists of androgen receptor in humans and wildlife via inapproprate binding to the receptor. |
topic |
Endocrine disruption Molecular docking Non-covalent interaction Nuclear receptor Polychlorinated dibenzofurans |
url |
http://www.sciencedirect.com/science/article/pii/S2666027X21000347 |
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