在Bradykinin中使用 ωBP-REMD模拟对联林Cis-Trans状态的综合分析
Maximilian Kienlein1, Martin Zacharias1, Maria M Reif1
1Center for Functional Protein Assemblies (CPA), Physics Department, Chair of Theoretical Biophysics (T38), Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748 Garching, Germany.
Journal of chemical theory and computation
|March 11, 2024
概括
氨酸的 cis-trans 异构化是蛋白质折叠的关键. 这项研究揭示了布拉迪基宁的合异构化状态,显示了一个proline的状态如何影响另一个,影响蛋白质结构.
科学领域:
- 生物化学 生化学
- 计算生物学 计算生物学
- 结构生物学 结构生物学
背景情况:
- 氨酸 (Pro) 的 cis-trans 异构化对于蛋白质的折叠和稳定性至关重要.
- 蛋白质中不同烯异构化状态之间的相互作用仍然不太清楚.
研究的目的:
- 作为一个模型系统,研究布拉迪基宁 (BK) 中三种普罗林残留物的合 cis-trans 异构化.
- 为了了解蛋白质适应过程中林异构体状态之间的构造性合.
主要方法:
- 使用了一种增强采样分子动力学方法: ω-bias潜在复制品交换分子动力学 (ωBP-REMD).
- 详尽地采样了所有proline异构体状态的组合.
- 执行了885 ns的模拟,以获得所有八种状态组合的趋同概率密度.
主要成果:
- 全转化状态被确定为zwitterionic水性BK的首选异构体,与实验数据一致.
- 其他同位素组合对结构组合做出了重大贡献.
- 揭示了proline异构化状态的相互依赖性,证明了不同proline异构体之间的合.
- 氨酸残留物的 cis/trans 均衡可以变化高达 2.5 kcal·mol-1,受其他氨酸残留物的状态的影响.
结论:
- ωBP-REMD 方法证明对采样林异构化状态的有效.
- 普林异构化状态的合可能在更大,结构受约束的蛋白质中发挥更重要的作用.
- 证明当Pro2切换到它的cis状态时,Pro7的cis状态变得更受欢迎.
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