Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens

Conrad Shyu; Timothy D Cavileer; James J Nagler; F Marty Ytreberg

doi:10.1016/j.taap.2010.11.005

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Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens

Journal article

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Peer reviewed

Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens

Conrad Shyu, Timothy D Cavileer, James J Nagler and F Marty Ytreberg

Toxicology and applied pharmacology, Vol.250(3), pp.322-326

02/01/2011

DOI: https://doi.org/10.1016/j.taap.2010.11.005

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https://hdl.handle.net/2376/112755

PMCID: PMC3022107

PMID: 21075131

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Abstract

Oncorhynchus mykiss - metabolism

Receptors, Estrogen - metabolism

Endocrine Disruptors - metabolism

Benzhydryl Compounds

Humans

Computational Biology

Ethinyl Estradiol - metabolism

Environmental Pollutants - metabolism

Phenols - metabolism

Raloxifene Hydrochloride - metabolism

Testosterone - metabolism

Atrazine - metabolism

Animals

Protein Isoforms - metabolism

In Vitro Techniques

Estradiol Congeners - metabolism

Environmental estrogens have been the subject of intense research due to their documented detrimental effects on the health of fish and wildlife and their potential to negatively impact humans. A complete understanding of how these compounds affect health is complicated because environmental estrogens are a structurally heterogeneous group of compounds. In this work, computational molecular dynamics simulations were utilized to predict the binding affinity of different compounds using rainbow trout (Oncorhynchus mykiss) estrogen receptors (ERs) as a model. Specifically, this study presents a comparison of the binding affinity of the natural ligand estradiol-17β to the four rainbow trout ER isoforms with that of three known environmental estrogens 17α-ethinylestradiol, bisphenol A, and raloxifene. Two additional compounds, atrazine and testosterone, that are known to be very weak or non-binders to ERs were tested. The binding affinity of these compounds to the human ERα subtype is also included for comparison. The results of this study suggest that, when compared to estradiol-17β, bisphenol A binds less strongly to all four receptors, 17α-ethinylestradiol binds more strongly, and raloxifene has a high affinity for the α subtype only. The results also show that atrazine and testosterone are weak or non-binders to the ERs. All of the results are in excellent qualitative agreement with the known in vivo estrogenicity of these compounds in the rainbow trout and other fishes. Computational estimation of binding affinities could be a valuable tool for predicting the impact of environmental estrogens in fish and other animals.

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Title: Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens
Creators: Conrad Shyu - Department of Physics, University of Idaho, Moscow, ID 83844-0903, USA
Timothy D Cavileer
James J Nagler
F Marty Ytreberg
Publication Details: Toxicology and applied pharmacology, Vol.250(3), pp.322-326
Academic Unit: UNKNOWN
Publisher: United States
Grant note: R21 GM083827-01A1 / NIGMS NIH HHS R21 GM083827 / NIGMS NIH HHS P20 RR016448-07S1 / NCRR NIH HHS R21GM083827 / NIGMS NIH HHS P20RR016448 / NCRR NIH HHS P20 RR016448 / NCRR NIH HHS
Identifiers: 99900547992601842
Language: English
Resource Type: Journal article