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Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts.
A number of environmental chemicals, by mimicking natural hormones, can disrupt endocrine function in experimental animals, wildlife, and humans. These chemicals, called "endocrine-disrupting chemicals" (EDCs), are such a scientific and public concern that screening and testing 58,000 chem...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2002
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240690/ https://www.ncbi.nlm.nih.gov/pubmed/11781162 |
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author | Hong, Huixiao Tong, Weida Fang, Hong Shi, Leming Xie, Qian Wu, Jie Perkins, Roger Walker, John D Branham, William Sheehan, Daniel M |
author_facet | Hong, Huixiao Tong, Weida Fang, Hong Shi, Leming Xie, Qian Wu, Jie Perkins, Roger Walker, John D Branham, William Sheehan, Daniel M |
author_sort | Hong, Huixiao |
collection | PubMed |
description | A number of environmental chemicals, by mimicking natural hormones, can disrupt endocrine function in experimental animals, wildlife, and humans. These chemicals, called "endocrine-disrupting chemicals" (EDCs), are such a scientific and public concern that screening and testing 58,000 chemicals for EDC activities is now statutorily mandated. Computational chemistry tools are important to biologists because they identify chemicals most important for in vitro and in vivo studies. Here we used a computational approach with integration of two rejection filters, a tree-based model, and three structural alerts to predict and prioritize estrogen receptor (ER) ligands. The models were developed using data for 232 structurally diverse chemicals (training set) with a 10(6) range of relative binding affinities (RBAs); we then validated the models by predicting ER RBAs for 463 chemicals that had ER activity data (testing set). The integrated model gave a lower false negative rate than any single component for both training and testing sets. When the integrated model was applied to approximately 58,000 potential EDCs, 80% (approximately 46,000 chemicals) were predicted to have negligible potential (log RBA < -4.5, with log RBA = 2.0 for estradiol) to bind ER. The ability to process large numbers of chemicals to predict inactivity for ER binding and to categorically prioritize the remainder provides one biologic measure to prioritize chemicals for entry into more expensive assays (most chemicals have no biologic data of any kind). The general approach for predicting ER binding reported here may be applied to other receptors and/or reversible binding mechanisms involved in endocrine disruption. |
format | Text |
id | pubmed-1240690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
record_format | MEDLINE/PubMed |
spelling | pubmed-12406902005-11-08 Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts. Hong, Huixiao Tong, Weida Fang, Hong Shi, Leming Xie, Qian Wu, Jie Perkins, Roger Walker, John D Branham, William Sheehan, Daniel M Environ Health Perspect Research Article A number of environmental chemicals, by mimicking natural hormones, can disrupt endocrine function in experimental animals, wildlife, and humans. These chemicals, called "endocrine-disrupting chemicals" (EDCs), are such a scientific and public concern that screening and testing 58,000 chemicals for EDC activities is now statutorily mandated. Computational chemistry tools are important to biologists because they identify chemicals most important for in vitro and in vivo studies. Here we used a computational approach with integration of two rejection filters, a tree-based model, and three structural alerts to predict and prioritize estrogen receptor (ER) ligands. The models were developed using data for 232 structurally diverse chemicals (training set) with a 10(6) range of relative binding affinities (RBAs); we then validated the models by predicting ER RBAs for 463 chemicals that had ER activity data (testing set). The integrated model gave a lower false negative rate than any single component for both training and testing sets. When the integrated model was applied to approximately 58,000 potential EDCs, 80% (approximately 46,000 chemicals) were predicted to have negligible potential (log RBA < -4.5, with log RBA = 2.0 for estradiol) to bind ER. The ability to process large numbers of chemicals to predict inactivity for ER binding and to categorically prioritize the remainder provides one biologic measure to prioritize chemicals for entry into more expensive assays (most chemicals have no biologic data of any kind). The general approach for predicting ER binding reported here may be applied to other receptors and/or reversible binding mechanisms involved in endocrine disruption. 2002-01 /pmc/articles/PMC1240690/ /pubmed/11781162 Text en |
spellingShingle | Research Article Hong, Huixiao Tong, Weida Fang, Hong Shi, Leming Xie, Qian Wu, Jie Perkins, Roger Walker, John D Branham, William Sheehan, Daniel M Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts. |
title | Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts. |
title_full | Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts. |
title_fullStr | Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts. |
title_full_unstemmed | Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts. |
title_short | Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts. |
title_sort | prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240690/ https://www.ncbi.nlm.nih.gov/pubmed/11781162 |
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