Zhang Peng Fei, Su Ji Guo
Key Laboratory for Microstructural Material Physics of Hebei Province, College of Science, Yanshan University, Qinhuangdao 066004, China.
J Chem Phys. 2019 Jul 28;151(4):045101. doi: 10.1063/1.5098542.
The elastic network model (ENM) is an effective method to extract the intrinsic dynamical properties encoded in protein tertiary structures. We have proposed a new ENM-based analysis method to reveal the motion modes directly responsible for a specific protein function, in which an internal coordinate related to the specific function was introduced to construct the internal/Cartesian hybrid coordinate space. In the present work, the function-related internal coordinates combined with a linear perturbation method were applied to identify the key sites controlling specific protein functional motions. The change in the fluctuations of the internal coordinate in response to residue perturbation was calculated in the hybrid coordinate space by using the linear response theory. The residues with the large fluctuation changes were identified to be the key sites that allosterically control the specific protein function. Two proteins, i.e., human DNA polymerase β and the chaperonin from Methanococcus maripaludis, were investigated as case studies, in which several collective and local internal coordinates were applied to identify the functionally key residues of these two studied proteins. The calculation results are consistent with the experimental observations. It is found that different collective internal coordinates lead to similar results, where the predicted functionally key sites are located at similar positions in the protein structure. While for the local internal coordinates, the predicted key sites tend to be situated at the region near to the coordinate-involving residues. Our studies provide a starting point for further exploring other function-related internal coordinates for other interesting proteins.
弹性网络模型（ENM）是一种从蛋白质三级结构中提取内在动力学特性的有效方法。我们提出了一种基于ENM的新分析方法，以揭示直接负责特定蛋白质功能的运动模式，该方法引入了与特定功能相关的内部坐标来构建内部/笛卡尔混合坐标空间。在本工作中，将与功能相关的内部坐标与线性微扰方法相结合，用于识别控制特定蛋白质功能运动的关键位点。利用线性响应理论，在混合坐标空间中计算了内部坐标响应残基微扰的波动变化。波动变化大的残基被确定为变构控制特定蛋白质功能的关键位点。以人类DNA聚合酶β和沼泽甲烷球菌伴侣蛋白这两种蛋白质为例进行了研究，其中应用了几种集体和局部内部坐标来识别这两种研究蛋白质的功能关键残基。计算结果与实验观察结果一致。研究发现，不同的集体内部坐标导致相似的结果，预测的功能关键位点位于蛋白质结构中的相似位置。而对于局部内部坐标，预测的关键位点往往位于靠近涉及坐标的残基的区域。我们 的研究为进一步探索其他有趣蛋白质的其他与功能相关的内部坐标提供了一个起点。
