在原子水平上捕获ABC输出器中的基质转移
Hendrik Göddeke1, Lars V Schäfer1
1Theoretical Chemistry, Faculty of Chemistry and Biochemistry, Ruhr University Bochum, 44780 Bochum, Germany.
Journal of the American Chemical Society
|June 25, 2020
概括
这项研究使用分子动力学模拟来可视化ATP结合盒 (ABC) 输送器如何将药物穿过膜. 它揭示了药物转移机制和基质与输送物和脂质双层的相互作用.
科学领域:
- 生物化学
- 结构生物学
- 计算生物学
背景情况:
- ATP结合盒 (ABC) 运输体是利用ATP水解来移动细胞膜中的基质的关键膜蛋白.
- 了解基质转移的原子级动态对于破译ABC传送机制至关重要.
研究的目的:
- 在原子层面阐明基质转移的动态机制.
- 调查异体ABC出口商TM287/288运输的多诺鲁比辛和维拉帕米尔.
主要方法:
- 用全原子分子动力学 (MD) 模拟来研究Thermotoga maritima的TM287/288传送器.
- 为了捕捉动态事件,在高温 (375K) 上进行了模拟.
主要成果:
- 在ABC输送器的交替接入形状变化 (向内转向向外) 后观察到基板转位.
- 由于差异性溶解效应,鲁比辛和维拉帕米尔从面向外的输送物释放到脂质双层中.
- 达努鲁比辛稳定地插入外侧说明书,而维拉帕米尔则表现出双层说明书之间的动态翻转.
结论:
- 这项研究为ABC传送器的化学机械合和基质转移过程提供了原子层面的见解.
- 与脂质双层的差异基质相互作用影响净运输效率,可能解释无用的运输周期.
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