Homology modeling to screen for potential binding of contaminants to thyroid hormone receptor and transthyretin in glaucous gull (Larus hyperboreus) and herring gull (Larus argentatus)
Thyroid hormone disrupting chemicals (THDCs) are of major concern in ecotoxicology. With the increased number of emerging chemicals on the market there is a need to screen for potential THDCs in a cost-efficient way, and in silico modeling is an alternative to address this issue. In this study homol...
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Online Access: | http://hdl.handle.net/11250/2644501 https://doi.org/10.1016/j.comtox.2020.100120 |
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ftntnutrondheimi:oai:ntnuopen.ntnu.no:11250/2644501 2023-05-15T14:59:17+02:00 Homology modeling to screen for potential binding of contaminants to thyroid hormone receptor and transthyretin in glaucous gull (Larus hyperboreus) and herring gull (Larus argentatus) Mortensen, Åse-Karen Mæhre, Silje Kristiansen, kurt Heimstad, Eldbjørg Sofie Gabrielsen, Geir W. Jenssen, Bjørn Munro Sylte, Ingebrigt 2020 http://hdl.handle.net/11250/2644501 https://doi.org/10.1016/j.comtox.2020.100120 eng eng Elsevier Computational Toxicology. 2020, 13 urn:issn:2468-1113 http://hdl.handle.net/11250/2644501 https://doi.org/10.1016/j.comtox.2020.100120 cristin:1798751 Navngivelse 4.0 Internasjonal http://creativecommons.org/licenses/by/4.0/deed.no CC-BY 13 Computational Toxicology Journal article Peer reviewed 2020 ftntnutrondheimi https://doi.org/10.1016/j.comtox.2020.100120 2020-03-04T23:32:26Z Thyroid hormone disrupting chemicals (THDCs) are of major concern in ecotoxicology. With the increased number of emerging chemicals on the market there is a need to screen for potential THDCs in a cost-efficient way, and in silico modeling is an alternative to address this issue. In this study homology modeling and docking was used to screen a list of 626 compounds for potential thyroid hormone disrupting properties in two gull species. The tested compounds were known contaminants or emerging contaminants predicted to have the potential to reach the Arctic. Models of transthyretin (TTR) and thyroid hormone receptor α and β (TRα and TRβ) from the Arctic top predator glaucous gull (Larus hyperboreus) and temperate predator herring gull (Larus argentatus) were constructed and used to predict the binding affinity of the compounds to the thyroid hormone (TH) binding sites. The modeling predicted that 28, 4 and 330 of the contaminants would bind to TRα, TRβ and TTR respectively. These compounds were in general halogenated, aromatic and had polar functional groups, like that of THs. However, the predicted binders did not necessarily have all these properties, such as the per- and polyfluoroalkyl substances that are not aromatic and still bind to the proteins. publishedVersion This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article in Journal/Newspaper Arctic Glaucous Gull Larus hyperboreus NTNU Open Archive (Norwegian University of Science and Technology) Arctic Computational Toxicology 13 100120 |
institution |
Open Polar |
collection |
NTNU Open Archive (Norwegian University of Science and Technology) |
op_collection_id |
ftntnutrondheimi |
language |
English |
description |
Thyroid hormone disrupting chemicals (THDCs) are of major concern in ecotoxicology. With the increased number of emerging chemicals on the market there is a need to screen for potential THDCs in a cost-efficient way, and in silico modeling is an alternative to address this issue. In this study homology modeling and docking was used to screen a list of 626 compounds for potential thyroid hormone disrupting properties in two gull species. The tested compounds were known contaminants or emerging contaminants predicted to have the potential to reach the Arctic. Models of transthyretin (TTR) and thyroid hormone receptor α and β (TRα and TRβ) from the Arctic top predator glaucous gull (Larus hyperboreus) and temperate predator herring gull (Larus argentatus) were constructed and used to predict the binding affinity of the compounds to the thyroid hormone (TH) binding sites. The modeling predicted that 28, 4 and 330 of the contaminants would bind to TRα, TRβ and TTR respectively. These compounds were in general halogenated, aromatic and had polar functional groups, like that of THs. However, the predicted binders did not necessarily have all these properties, such as the per- and polyfluoroalkyl substances that are not aromatic and still bind to the proteins. publishedVersion This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
format |
Article in Journal/Newspaper |
author |
Mortensen, Åse-Karen Mæhre, Silje Kristiansen, kurt Heimstad, Eldbjørg Sofie Gabrielsen, Geir W. Jenssen, Bjørn Munro Sylte, Ingebrigt |
spellingShingle |
Mortensen, Åse-Karen Mæhre, Silje Kristiansen, kurt Heimstad, Eldbjørg Sofie Gabrielsen, Geir W. Jenssen, Bjørn Munro Sylte, Ingebrigt Homology modeling to screen for potential binding of contaminants to thyroid hormone receptor and transthyretin in glaucous gull (Larus hyperboreus) and herring gull (Larus argentatus) |
author_facet |
Mortensen, Åse-Karen Mæhre, Silje Kristiansen, kurt Heimstad, Eldbjørg Sofie Gabrielsen, Geir W. Jenssen, Bjørn Munro Sylte, Ingebrigt |
author_sort |
Mortensen, Åse-Karen |
title |
Homology modeling to screen for potential binding of contaminants to thyroid hormone receptor and transthyretin in glaucous gull (Larus hyperboreus) and herring gull (Larus argentatus) |
title_short |
Homology modeling to screen for potential binding of contaminants to thyroid hormone receptor and transthyretin in glaucous gull (Larus hyperboreus) and herring gull (Larus argentatus) |
title_full |
Homology modeling to screen for potential binding of contaminants to thyroid hormone receptor and transthyretin in glaucous gull (Larus hyperboreus) and herring gull (Larus argentatus) |
title_fullStr |
Homology modeling to screen for potential binding of contaminants to thyroid hormone receptor and transthyretin in glaucous gull (Larus hyperboreus) and herring gull (Larus argentatus) |
title_full_unstemmed |
Homology modeling to screen for potential binding of contaminants to thyroid hormone receptor and transthyretin in glaucous gull (Larus hyperboreus) and herring gull (Larus argentatus) |
title_sort |
homology modeling to screen for potential binding of contaminants to thyroid hormone receptor and transthyretin in glaucous gull (larus hyperboreus) and herring gull (larus argentatus) |
publisher |
Elsevier |
publishDate |
2020 |
url |
http://hdl.handle.net/11250/2644501 https://doi.org/10.1016/j.comtox.2020.100120 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic Glaucous Gull Larus hyperboreus |
genre_facet |
Arctic Glaucous Gull Larus hyperboreus |
op_source |
13 Computational Toxicology |
op_relation |
Computational Toxicology. 2020, 13 urn:issn:2468-1113 http://hdl.handle.net/11250/2644501 https://doi.org/10.1016/j.comtox.2020.100120 cristin:1798751 |
op_rights |
Navngivelse 4.0 Internasjonal http://creativecommons.org/licenses/by/4.0/deed.no |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1016/j.comtox.2020.100120 |
container_title |
Computational Toxicology |
container_volume |
13 |
container_start_page |
100120 |
_version_ |
1766331393811415040 |