通过分子对接,动力学模拟和成像,对人类nAChRs中的neonicotinoids和N-unsubstituted代谢物的结构洞察力
Karin Grillberger1, Eike Cöllen2, Claudia Immacolata Trivisani3
1Department of Pharmaceutical Sciences, University of Vienna, 1090 Vienna, Austria.
International journal of molecular sciences
|September 9, 2023
概括
类农药可能通过与尼古丁乙胆受体 (nAChRs) 相互作用而影响人类神经元. 这项研究使用了计算和基于细胞的方法来评估这些毒性影响,支持更安全的农药开发.
科学领域:
- 毒理学 毒理学 毒理学
- 神经科学是一个神经科学.
- 计算化学计算化学
背景情况:
- 尼奥尼古丁类药物向昆虫的尼古丁酸乙胆受体 (nAChRs).
- 人们对新烟类药物对人类nAChRs的影响存在担忧.
- 新方法方法 (NAM) 对于下一代风险评估 (NGRA) 是至关重要的.
研究的目的:
- 研究neonicotinoids和代谢物对人类神经元的潜在毒性影响.
- 使用in silico和in vitro方法来取代动物试验.
- 评估与人类nAChR异型α7和α3β4.4的相互作用.
主要方法:
- 组合对接研究以确定分子启动事件 (MIE).
- 分子动力学 (MD) 模拟和结合能计算用于姿势改进.
- 在LUHMES神经元上进行成像,以确认关键事件 (KE) 和激应效应.
主要成果:
- 确定了新烟类药物/代谢物和人类nAChR异型之间的潜在MIE相互作用.
- 精细的对接姿势和计算的结合能量.
- 在人类神经元中确认了下游的KEEs和descyano-thiacloprid (DCNT) 的激动作用.
结论:
- 结合的in silico和in vitro方法有效地评估了类毒素的神经毒性.
- 这一基于NAM的战略支持NGRA在农药安全方面.
- 验证了代谢物DCNT对人类神经元的激动作用.
相关概念视频
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