Acceleration of cryo-EM Flexible Fitting for Large Biomolecular Systems by Efficient Space Partitioning
Acceleration of cryo-EM Flexible Fitting for Large Biomolecular Systems by Efficient Space Partitioning
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DOI：
10.1016/j.str.2018.09.004
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发表时间：
2019-01-02
期刊：
影响因子：
5.7
通讯作者：
Sugita, Yuji
中科院分区：
文献类型：
--
作者：
Mori, Takaharu;Kulik, Marta;Sugita, Yuji
柔性拟合是从冷冻电子显微镜（cryo-EM）密度图构建生物分子3D结构的强大技术。一种流行的方法是基于互相关系数的方法，其中分子动力学（MD）模拟是用包括实验和模拟密度图之间的互相关系数的偏置势进行的。在这里，我们提出了有效的并行化计划的互相关系数的计算，以加速灵活的拟合。我们的方案使用CPU和混合CPU + GPU架构针对小型、中型和大型生物分子进行了测试。原子分解分子动力学模型适用于小分子蛋白质，如Ca ~（2+）-ATP酶，而区域分解分子动力学模型适用于大分子系统，如核糖体，如全原子Go模型或全原子显式溶剂模型。我们的方法允许灵活的拟合各种生物分子与合理的计算成本。这种方法还将高分辨率结构精修与蛋白质结构-功能关系的研究联系起来。
Flexible fitting is a powerful technique to build the 3D structures of biomolecules from cryoelectron microscopy (cryo-EM) density maps. One popular method is a cross-correlation coefficient-based approach, where the molecular dynamics (MD) simulation is carried out with the biasing potential that includes the cross-correlation coefficient between the experimental and simulated density maps. Here, we propose efficient parallelization schemes for the calculation of the cross-correlation coefficient to accelerate flexible fitting. Our schemes are tested for small, medium, and large biomolecules using CPU and hybrid CPU + GPU architectures. The scheme for the atomic decomposition MD is suitable for small proteins such as Ca2+-ATPase with the all-atom Go model, while that for the domain decomposition MD is better for larger systems such as ribosome with the all-atom Go or the all-atom explicit solvent models. Our methods allow flexible fitting for various biomolecules with reasonable computational cost. This approach also connects high-resolution structure refinements with investigation of protein structure-function relationship.