Atomistic View of the Conformational Activation of Src Kinase Using the String Method with Swarms-of-Trajectories
Atomistic View of the Conformational Activation of Src Kinase Using the String Method with Swarms-of-Trajectories
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DOI：
10.1016/j.bpj.2009.06.016
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发表时间：
2009-08-19
影响因子：
3.4
通讯作者：
Roux, Benoit
中科院分区：
文献类型：
--
作者：
Gan, Wenxun;Yang, Sichun;Roux, Benoit
采用全原子显式溶剂分子动力学模拟的轨迹群串方法，研究了人c-Src酪氨酸激酶催化结构域从无活性到有活性的构象转变。激活过程分为两个主要步骤，首先激活环（a环）打开，然后是α - C螺旋的旋转。沿激活路径计算的平均力能势显示出局部最小值，从而可以识别中间状态。这些结果表明，具有轨迹群的弦方法是表征大型生物分子系统中复杂和缓慢构象转变的有效技术。
The inactive-to-active conformational transition of the catalytic domain of human c-Src tyrosine kinase is characterized using the string method with swarms-of-trajectories with all-atom explicit solvent molecular dynamics simulations. The activation process occurs in two main steps in which the activation loop (A-loop) opens first, followed by the rotation of the alpha C helix. The computed potential of mean force energy along the activation pathway displays a local minimum, which allows the identification of an intermediate state. These results show that the string method with swarms-of -trajectories is an effective technique to characterize complex and slow conformational transitions in large biomolecular systems.