Comparison between slow anisotropic LE4PD fluctuations and the principal component analysis modes of ubiquitin
Comparison between slow anisotropic LE4PD fluctuations and the principal component analysis modes of ubiquitin
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DOI：
10.1063/5.0041211
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发表时间：
2021-03-28
影响因子：
4.4
通讯作者：
Guenza, M. G.
中科院分区：
文献类型：
--
作者：
Beyerle, E. R.;Guenza, M. G.
蛋白质的生物学功能和折叠机制往往是由大规模的慢运动引导的，这涉及到跨越高能量垒。在模拟轨迹中，通常使用主成分分析（PCA）来识别这些缓慢波动。尽管这种方法很受欢迎，但迄今为止，对其基于蛋白质运动物理学的预测的完整分析仍然有限。本研究将PCA与蛋白质动力学的Langevin模型正式联系起来，并分析了能量障碍和流体动力相互作用对缓慢PCA运动模式的贡献。为此，我们引入了蛋白质动力学的朗之万方程的各向异性扩展，称为LE4PD-XYZ，它正式连接到PCA“基本动力学”。LE4PD-XYZ是一种精确的粗粒度扩散方法来模拟蛋白质运动，它描述了蛋白质α碳的各向异性波动。LE4PD解释了流体动力效应和模式相关的自由能势垒。本研究将LE4PD-XYZ识别的大规模各向异性波动与模式相关的PCA预测进行了比较，从蛋白质泛素的微秒长α碳分子动力学原子轨迹开始。我们观察到自由能垒和流体动力相互作用的包含对泛素慢模式的识别和时间尺度有重要影响。
The biological function and folding mechanisms of proteins are often guided by large-scale slow motions, which involve crossing high energy barriers. In a simulation trajectory, these slow fluctuations are commonly identified using a principal component analysis (PCA). Despite the popularity of this method, a complete analysis of its predictions based on the physics of protein motion has been so far limited. This study formally connects the PCA to a Langevin model of protein dynamics and analyzes the contributions of energy barriers and hydrodynamic interactions to the slow PCA modes of motion. To do so, we introduce an anisotropic extension of the Langevin equation for protein dynamics, called the LE4PD-XYZ, which formally connects to the PCA "essential dynamics." The LE4PD-XYZ is an accurate coarse-grained diffusive method to model protein motion, which describes anisotropic fluctuations in the alpha carbons of the protein. The LE4PD accounts for hydrodynamic effects and mode-dependent free-energy barriers. This study compares large-scale anisotropic fluctuations identified by the LE4PD-XYZ to the mode-dependent PCA predictions, starting from a microsecond-long alpha carbon molecular dynamics atomistic trajectory of the protein ubiquitin. We observe that the inclusion of free-energy barriers and hydrodynamic interactions has important effects on the identification and timescales of ubiquitin's slow modes.