Xiangqiao Li, Huihui Liu, Songshan Zhao, Peter Watson, Xianhai Yang
{"title":"典型新兴污染物与 Gobiocypris rarus 转甲状腺素的结合相互作用:体外和硅学研究","authors":"Xiangqiao Li, Huihui Liu, Songshan Zhao, Peter Watson, Xianhai Yang","doi":"10.1007/s11783-024-1895-1","DOIUrl":null,"url":null,"abstract":"<p>Emerging contaminants (ECs) have drawn global concern, and the endocrine disrupting chemicals is one of the highly interested ECs categories. However, numerous ECs lacks the basic information about whether they can disturb the endocrine related biomacromolecules or elicit endocrine related detrimental effects on organism. In this study, the potential binding affinity and underlying binding mechanism between 29 ECs from 7 chemical groups and <i>Gobiocypris rarus</i> transthyretin (CrmTTR) are investigated and probed using <i>in vitro</i> and <i>in silico</i> methods. The experimental results demonstrate that 14 selected ECs (11 disinfection byproducts, 1 pharmaceuticals and personal care product, 1 alkylphenol, 1 perfluoroalkyl and polyfluoroalkyl substance) are potential CrmTTR binders. The CrmTTR binding affinity of three ECs (i.e., 2,6-diiodo-4-nitrophenol (log<i>RP</i>(T<sub>4</sub>) = 0.678 ± 0.198), 2-bromo-6-chloro-4-nitrophenol (log<i>RP</i>(T<sub>4</sub>) = 0.399 ± 0.0908), tetrachloro-1,4-benzoquinone (log<i>RP</i>(T<sub>4</sub>) = 0.272 ± 0.0655)) were higher than that of 3,3′,5,5′-tetraiodo-L-thyronine, highlighting that more work should be performed to reveal their potential endocrine related harmful effects on <i>Gobiocypris rarus</i>. Molecular docking results imply that hydrogen bond and hydrophobic interactions are the dominated non-covalent interactions between the active disruptors and CrmTTR. The optimum mechanism-based (for CrmTTR), and high throughput screening (for CrmTTR, little skate-TTR, seabream-TTR, and human-TTR) binary classification models are developed using three machine learning algorithms, and all the models have good classification performance. To facilitate the use of developed high throughput screening models, a tool named “TTR Profiler” is derived, which could be employed to determine whether a given substance is a potential CrmTTR, little skate-TTR, seabream-TTR, or human-TTR disruptor or not.</p>","PeriodicalId":12720,"journal":{"name":"Frontiers of Environmental Science & Engineering","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Binding interaction of typical emerging contaminants on Gobiocypris rarus transthyretin: an in vitro and in silico study\",\"authors\":\"Xiangqiao Li, Huihui Liu, Songshan Zhao, Peter Watson, Xianhai Yang\",\"doi\":\"10.1007/s11783-024-1895-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Emerging contaminants (ECs) have drawn global concern, and the endocrine disrupting chemicals is one of the highly interested ECs categories. However, numerous ECs lacks the basic information about whether they can disturb the endocrine related biomacromolecules or elicit endocrine related detrimental effects on organism. In this study, the potential binding affinity and underlying binding mechanism between 29 ECs from 7 chemical groups and <i>Gobiocypris rarus</i> transthyretin (CrmTTR) are investigated and probed using <i>in vitro</i> and <i>in silico</i> methods. The experimental results demonstrate that 14 selected ECs (11 disinfection byproducts, 1 pharmaceuticals and personal care product, 1 alkylphenol, 1 perfluoroalkyl and polyfluoroalkyl substance) are potential CrmTTR binders. The CrmTTR binding affinity of three ECs (i.e., 2,6-diiodo-4-nitrophenol (log<i>RP</i>(T<sub>4</sub>) = 0.678 ± 0.198), 2-bromo-6-chloro-4-nitrophenol (log<i>RP</i>(T<sub>4</sub>) = 0.399 ± 0.0908), tetrachloro-1,4-benzoquinone (log<i>RP</i>(T<sub>4</sub>) = 0.272 ± 0.0655)) were higher than that of 3,3′,5,5′-tetraiodo-L-thyronine, highlighting that more work should be performed to reveal their potential endocrine related harmful effects on <i>Gobiocypris rarus</i>. Molecular docking results imply that hydrogen bond and hydrophobic interactions are the dominated non-covalent interactions between the active disruptors and CrmTTR. The optimum mechanism-based (for CrmTTR), and high throughput screening (for CrmTTR, little skate-TTR, seabream-TTR, and human-TTR) binary classification models are developed using three machine learning algorithms, and all the models have good classification performance. To facilitate the use of developed high throughput screening models, a tool named “TTR Profiler” is derived, which could be employed to determine whether a given substance is a potential CrmTTR, little skate-TTR, seabream-TTR, or human-TTR disruptor or not.</p>\",\"PeriodicalId\":12720,\"journal\":{\"name\":\"Frontiers of Environmental Science & Engineering\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers of Environmental Science & Engineering\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://doi.org/10.1007/s11783-024-1895-1\",\"RegionNum\":2,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENGINEERING, ENVIRONMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers of Environmental Science & Engineering","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1007/s11783-024-1895-1","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENGINEERING, ENVIRONMENTAL","Score":null,"Total":0}
Binding interaction of typical emerging contaminants on Gobiocypris rarus transthyretin: an in vitro and in silico study
Emerging contaminants (ECs) have drawn global concern, and the endocrine disrupting chemicals is one of the highly interested ECs categories. However, numerous ECs lacks the basic information about whether they can disturb the endocrine related biomacromolecules or elicit endocrine related detrimental effects on organism. In this study, the potential binding affinity and underlying binding mechanism between 29 ECs from 7 chemical groups and Gobiocypris rarus transthyretin (CrmTTR) are investigated and probed using in vitro and in silico methods. The experimental results demonstrate that 14 selected ECs (11 disinfection byproducts, 1 pharmaceuticals and personal care product, 1 alkylphenol, 1 perfluoroalkyl and polyfluoroalkyl substance) are potential CrmTTR binders. The CrmTTR binding affinity of three ECs (i.e., 2,6-diiodo-4-nitrophenol (logRP(T4) = 0.678 ± 0.198), 2-bromo-6-chloro-4-nitrophenol (logRP(T4) = 0.399 ± 0.0908), tetrachloro-1,4-benzoquinone (logRP(T4) = 0.272 ± 0.0655)) were higher than that of 3,3′,5,5′-tetraiodo-L-thyronine, highlighting that more work should be performed to reveal their potential endocrine related harmful effects on Gobiocypris rarus. Molecular docking results imply that hydrogen bond and hydrophobic interactions are the dominated non-covalent interactions between the active disruptors and CrmTTR. The optimum mechanism-based (for CrmTTR), and high throughput screening (for CrmTTR, little skate-TTR, seabream-TTR, and human-TTR) binary classification models are developed using three machine learning algorithms, and all the models have good classification performance. To facilitate the use of developed high throughput screening models, a tool named “TTR Profiler” is derived, which could be employed to determine whether a given substance is a potential CrmTTR, little skate-TTR, seabream-TTR, or human-TTR disruptor or not.
期刊介绍:
Frontiers of Environmental Science & Engineering (FESE) is an international journal for researchers interested in a wide range of environmental disciplines. The journal''s aim is to advance and disseminate knowledge in all main branches of environmental science & engineering. The journal emphasizes papers in developing fields, as well as papers showing the interaction between environmental disciplines and other disciplines.
FESE is a bi-monthly journal. Its peer-reviewed contents consist of a broad blend of reviews, research papers, policy analyses, short communications, and opinions. Nonscheduled “special issue” and "hot topic", including a review article followed by a couple of related research articles, are organized to publish novel contributions and breaking results on all aspects of environmental field.