Free energy of conformational transition paths in biomolecules: The string method and its application to myosin VI
Free energy of conformational transition paths in biomolecules: The string method and its application to myosin VI
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DOI：
10.1063/1.3544209
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发表时间：
2011-02-28
影响因子：
4.4
通讯作者：
Vanden-Eijnden, Eric
中科院分区：
文献类型：
--
作者：
Ovchinnikov, Victor;Karplus, Martin;Vanden-Eijnden, Eric
在弦法的框架下开发的一套技术与全原子分子动力学模拟相结合，分析肌球蛋白 VI 转换器域的前动力冲程 (PPS) 和严格 (R) 结构之间的构象变化。详细讨论了将这些技术应用于如此大而复杂的生物分子所面临的具体挑战。这些挑战包括（i）确定一组适当的集体变量来应用弦方法，（ii）找到合适的初始弦，（iii）获得沿跃迁路径的自由能的收敛分布，（iv）验证和解释自由能分布，以及（v）计算跃迁的平均首次通过时间。 PPS 的详细说明。获得肌球蛋白 VI 转换器域中的 R 跃迁，包括跃迁路径、沿路径的自由能和相互转换速率。这里开发的方法预计将在复杂生物分子构象转变的研究中更普遍地有用。 (C) 2011 年美国物理研究所。 [doi:10.1063/1.3544209]
A set of techniques developed under the umbrella of the string method is used in combination with all-atom molecular dynamics simulations to analyze the conformation change between the prepower-stroke (PPS) and rigor (R) structures of the converter domain of myosin VI. The challenges specific to the application of these techniques to such a large and complex biomolecule are addressed in detail. These challenges include (i) identifying a proper set of collective variables to apply the string method, (ii) finding a suitable initial string, (iii) obtaining converged profiles of the free energy along the transition path, (iv) validating and interpreting the free energy profiles, and (v) computing the mean first passage time of the transition. A detailed description of the PPS. R transition in the converter domain of myosin VI is obtained, including the transition path, the free energy along the path, and the rates of interconversion. The methodology developed here is expected to be useful more generally in studies of conformational transitions in complex biomolecules. (C) 2011 American Institute of Physics. [doi:10.1063/1.3544209]