从过渡路径理论模拟中,CO进入,内部扩散和出口在肌球蛋白中的全部动力学
Tang-Qing Yu1, Mauro Lapelosa, Eric Vanden-Eijnden
1Courant Institute of Mathematical Sciences, New York University , New York, New York 10012, United States.
Journal of the American Chemical Society
|February 10, 2015
概括
马科维亚的里程碑分子动力学 (MD) 模拟与过渡路径理论 (TPT) 结合,揭示了肌球蛋白中的CO结合动力学. 这种方法准确地模拟了CO的进入,退出和内部运动,确定了histidine门作为一个关键路径.
科学领域:
- 生物物理学的生物物理.
- 计算化学计算化学
- 分子动力学分子动力学
背景情况:
- 了解肌球蛋白等蛋白质中的联结体动力学对于破译生物功能至关重要.
- 传统的分子动力学 (MD) 模拟在捕捉缓慢的动力事件方面存在局限性.
研究的目的:
- 开发和应用一个计算框架,以准确估计肌球蛋白内联体 (CO) 运动的动力学.
- 确定控制二氧化碳进入,退出和内部站点跳转的关键途径和机制.
主要方法:
- 马科维亚的里程碑分子动力学 (MD) 模拟在一个集体变量空间模块化.
- 使用过渡路径理论 (TPT) 定义最佳里程碑的自由能量表面分析.
- 将运动模型粗地分为生物学相关的空腔和三态方案.
主要成果:
- 准确估计CO进出率,显示与实验数据的半定量一致.
- 鉴定胺门 (H64) 是溶剂和远端口袋 (≈90%) 之间的二氧化碳流的主要通道.
- 阐明了一种连续的,相互依赖的"启动"机制,使CO通过histidine门逃逸.
结论:
- 过渡路径理论 (TPT) 模拟有效地克服了标准MD的时间尺度限制.
- 这种基于TPT的方法提供了一种可靠的方法来估计生物分子中的转变机制和转变稳定状态之间的速率.
- 这项研究提供了关于肌球蛋白内连接体的动态行为的重要见解.
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