对针对L-FABP的PFAS进行肝毒性评估调查,使用结合性亲和数据和基于机器学习的QSAR模型
Jiayi Zhao1, Xiaoyue Shi2, Zhiqin Wang2
1Department of Medical Chemistry, School of Pharmacy, Qingdao University, Qingdao 266071, China; Department of Occupational and Environmental Health, School of Public Health, Qingdao University, Qingdao 266071, China.
Ecotoxicology and environmental safety
|July 31, 2023
概括
和多醇基物质 (PFAS) 通过与肝脂肪酸结合蛋白 (L-FABP) 结合,可能会损害肝脏. 这项研究开发了一个机器学习模型来预测危险的PFAS,确定分子灵活性是它们毒性的关键因素.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 计算化学计算化学
背景情况:
- 和多醇基物质 (PFAS) 是全球发现的持久性有机污染物.
- 评估PFAS的安全性,特别是其肝毒性,是一项挑战.
- PFASs可能会在肝脏中积累,并通过与肝脏脂肪酸结合蛋白 (L-FABP) 相互作用而导致损伤.
研究的目的:
- 为了评估各种PFAS与L-FABP的结合亲和力.
- 开发一种用于识别潜在危险 PFAS 的预测模型.
- 了解影响PFAS诱导肝毒性的分子特性.
主要方法:
- 对两个L-FABP结合部位的计算分析.
- 使用机器学习开发定量结构-活动关系 (QSAR) 模型.
- 贝叶斯核机器回归 (BKMR) 的应用,以确定决定性分子性质.
主要成果:
- L-FABP的内部部位对PFAS敏感性更高,对不同的PFAS化学品类有特定的亲和力.
- 一个QSAR模型已成功开发,用于预测PFAS肝毒性.
- 分子灵活性被确定为PFAS诱导的肝毒性的一个关键因素,通过个人和联合作用影响结合亲和力.
结论:
- 了解PFAS与L-FABP的结合对于评估肝毒性至关重要.
- 开发的QSAR模型为预测危险的PFAS提供了一种有效的方法.
- 确定分子灵活性作为一个关键决定因素,为风险评估和开发更安全的替代品提供了洞察力.
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