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

IF 6.1 2区 环境科学与生态学 Q2 ENGINEERING, ENVIRONMENTAL
Xiangqiao Li, Huihui Liu, Songshan Zhao, Peter Watson, Xianhai Yang
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引用次数: 0

摘要

新出现的污染物(ECs)已引起全球关注,而干扰内分泌的化学物质是备受关注的 ECs 类别之一。然而,众多的ECs是否会扰乱与内分泌相关的生物大分子或对生物体产生与内分泌相关的有害影响,目前还缺乏基本的信息。本研究采用体外和硅学方法,研究和探讨了 7 个化学组的 29 种氨基甲酸乙酯与 Gobiocypris rarus transthyretin(CrmTTR)之间的潜在结合亲和力和基本结合机制。实验结果表明,所选的 14 种氨基甲酸乙酯(11 种消毒副产品、1 种药品和个人护理产品、1 种烷基酚、1 种全氟烷基和多氟烷基物质)是潜在的 CrmTTR 结合剂。三种 EC 的 CrmTTR 结合亲和力(即2,6-二碘-4-硝基苯酚(logRP(T4) = 0.678 ± 0.198)、2-溴-6-氯-4-硝基苯酚(logRP(T4) = 0.399 ± 0.0908)、四氯-1,4-苯醌(logRP(T4) = 0.272 ± 0.0655))均高于 3,3′,5,5′-四碘-L-吡ronine,这表明应开展更多的工作来揭示它们对豚鼠内分泌相关的潜在有害影响。分子对接结果表明,氢键和疏水相互作用是活性干扰物与 CrmTTR 之间主要的非共价相互作用。利用三种机器学习算法建立了基于机理的(CrmTTR)和高通量筛选的(CrmTTR、小鳐鱼-TTR、鲷鱼-TTR和人-TTR)最佳二元分类模型,所有模型都具有良好的分类性能。为便于使用所开发的高通量筛选模型,还开发了一种名为 "TTR Profiler "的工具,可用于确定给定物质是否是潜在的 CrmTTR、小鳐鱼-TTR、鲷鱼-TTR 或人类-TTR 干扰物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Binding interaction of typical emerging contaminants on Gobiocypris rarus transthyretin: an in vitro and in silico study

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.

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来源期刊
Frontiers of Environmental Science & Engineering
Frontiers of Environmental Science & Engineering ENGINEERING, ENVIRONMENTAL-ENVIRONMENTAL SCIENCES
CiteScore
10.90
自引率
12.50%
发文量
988
审稿时长
6.1 months
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.
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