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

Abstract

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-17{beta} to the four rainbow trout ER isoforms with that of three known environmental estrogens 17{alpha}-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 ER{alpha} subtype is also included for comparison. The results of this study suggest that, when compared to estradiol-17{beta}, bisphenol A binds less strongly to all four receptors, 17{alpha}-ethinylestradiol binds more strongly, and raloxifene has a high affinity for the {alpha} subtype only. The results also show that atrazine and testosterone are weak or non-binders to the ERs. All of themore » 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.« less

Authors:
 [1]; ;  [2];  [1]
  1. Department of Physics, University of Idaho, Moscow, ID 83844-0903 (United States)
  2. Department of Biological Sciences and Center for Reproductive Biology, University of Idaho, Moscow, ID 83844-3051 (United States)
Publication Date:
OSTI Identifier:
21535229
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 250; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2010.11.005; PII: S0041-008X(10)00430-8; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AFFINITY; ESTRADIOL; HUMAN POPULATIONS; IN VIVO; MOLECULAR DYNAMICS METHOD; RECEPTORS; SIMULATION; TESTOSTERONE; TROUT; ANDROGENS; ANDROSTANES; ANIMALS; AQUATIC ORGANISMS; CALCULATION METHODS; ESTRANES; ESTROGENS; FISHES; HORMONES; HYDROXY COMPOUNDS; KETONES; MEMBRANE PROTEINS; ORGANIC COMPOUNDS; POPULATIONS; PROTEINS; STEROID HORMONES; STEROIDS; VERTEBRATES

Citation Formats

Shyu, Conrad, Cavileer, Timothy D., Nagler, James J., and Ytreberg, F. Marty, E-mail: ytreberg@uidaho.edu. Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens. United States: N. p., 2011. Web. doi:10.1016/j.taap.2010.11.005.
Shyu, Conrad, Cavileer, Timothy D., Nagler, James J., & Ytreberg, F. Marty, E-mail: ytreberg@uidaho.edu. Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens. United States. doi:10.1016/j.taap.2010.11.005.
Shyu, Conrad, Cavileer, Timothy D., Nagler, James J., and Ytreberg, F. Marty, E-mail: ytreberg@uidaho.edu. Tue . "Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens". United States. doi:10.1016/j.taap.2010.11.005.
@article{osti_21535229,
title = {Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens},
author = {Shyu, Conrad and Cavileer, Timothy D. and Nagler, James J. and Ytreberg, F. Marty, E-mail: ytreberg@uidaho.edu},
abstractNote = {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-17{beta} to the four rainbow trout ER isoforms with that of three known environmental estrogens 17{alpha}-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 ER{alpha} subtype is also included for comparison. The results of this study suggest that, when compared to estradiol-17{beta}, bisphenol A binds less strongly to all four receptors, 17{alpha}-ethinylestradiol binds more strongly, and raloxifene has a high affinity for the {alpha} 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.},
doi = {10.1016/j.taap.2010.11.005},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 250,
place = {United States},
year = {2011},
month = {2}
}