分子动态模拟揭示了表皮生长因子受体与香烯的分子相互作用与致癌性有关
Huaxing Fei1,2, Wen Li1,2, Nan Lu1,2
1Institute of Electromagnetics and Acoustics, Department of Electronic Science, Xiamen University Xiamen 361005 P. R. China 15079534562@163.com zhangyouyu@xmu.edu.cn.
RSC advances
|June 2, 2023
概括
Musk xylene (MX) 通过与肝细胞中的表皮生长因子受体 (EGFR) 结合,激活MAPK通路,可能导致癌症. 这种相互作用模仿了自然连接体,可能导致瘤发生.
科学领域:
- 环境毒理学环境毒理学
- 分子生物学分子生物学
- 计算化学是一种计算化学.
背景情况:
- Musk xylene (MX) 是一种新兴的环境污染物,存在于个人护理产品中.
- 长期暴露于MX与各种癌症有关,但潜在的机制尚不清楚.
- 之前的研究表明,MX暴露会诱导恶性肝细胞转化,并上调MAPK通路基因,包括EGFR.
研究的目的:
- 通过分子动力学 (MD) 模拟来研究氧烯 (MX) 和表皮生长因子受体 (EGFR) 之间的相互作用机制.
- 阐明MX与EGFR结合如何可能导致瘤发生.
- 为了确定潜在的结合点和相互作用,以便进一步实验验证.
主要方法:
- 用分子动力学 (MD) 模拟来建模MX与EGFR细胞外域 (ECD) 之间的相互作用.
- 分析了结合亲和关系和相互作用类型 (范德瓦尔斯,非极性).
- 使用MM/PBSA方法预测结合地点的热残留物.
主要成果:
- 发现MX与EGFR ECD上的四个不同的位点结合,最强的亲和力在位点sIII.
- 主要的结合力是范德瓦尔斯和非极性相互作用.
- 网站sIII,MX结合最强的地方,与EGF的结合区域重叠,EGFR的天然连接体.
结论:
- 通过与EGFR结合,MX可能会激活MAPK信号通路,这种方式与其天然连接体EGF类似.
- 这种相互作用机制为MX诱导的肝细胞恶性转变和瘤发生提供了潜在的解释.
- 识别热残留物为MX致癌的未来实验研究提供了理论指导.
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