Coarse-Grained Langevin Equation for Protein Dynamics: Global Anisotropy and a Mode Approach to Local Complexity
Coarse-Grained Langevin Equation for Protein Dynamics: Global Anisotropy and a Mode Approach to Local Complexity
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DOI：
10.1021/jp509473z
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发表时间：
2015-07-23
影响因子：
3.3
通讯作者：
Guenza, M. G.
中科院分区：
文献类型：
--
作者：
Copperman, J.;Guenza, M. G.
我们利用多尺度方法进行分子动力学模拟，以获得定量结构平均值，作为蛋白质动力学的粗粒度朗之万方程的输入，该方程可以解析求解。该方法将蛋白质描述为基本上是半柔性的物体，坍缩成代表折叠态的自由能。朗之万方程的正模解析解自然地分为描述大分子作为一个整体的完全各向异性翻滚的全局模式和描述折叠结构的局部波动的内部模式。大分子构型自由能景观的复杂性导致内部模式的重整化，而全局模式提供了一个基础集，在与实验比较时可以解释偶极取向和全局各向异性。这种简单的方法预测了从皮秒到纳秒的全局旋转扩散和内部运动的动力学，并且与分子动力学模拟计算的时间相关函数相比是定量的，并且与核磁共振弛豫实验很好地一致。这种方法的基础是将内部耗散,这是没有任何刚体流动的建模方案。
We utilize a multiscale approach where molecular dynamic simulations ate performed to obtain quantitative structural averages used as input to a coarse-grained Langevin equation for protein dynamics, which can be solved analytically. The approach describes proteins as fundamentally semiflexible objects collapsed into the free energy well representing the folded state. The normal-mode analytical solution to this Langevin equation naturally separates into global modes describing the fully anisotropic tumbling of the macromolecule as a whole and internal modes which describe local fluctuations about the folded structure. Complexity in the configurational free-energy landscape of the macromolecule leads to a renormalization of the internal modes, while the global modes provide a basis set in which the dipolar orientation and global anisotropy can be accounted for when comparing to experiments. This simple approach predicts the dynamics of both global rotational diffusion and internal motion from the picosecond to the nanosecond regime and is quantitative when compared to time correlation functions calculated from molecular dynamic simulations and in good agreement with nuclear magnetic resonance relaxation experiments. Fundamental to this approach is the inclusion of internal dissipation, which is absent in any rigid-body hydrodynamical modeling scheme.