Automated cryo-EM structure refinement using correlation-driven molecular dynamics
Automated cryo-EM structure refinement using correlation-driven molecular dynamics
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DOI：
10.7554/elife.43542
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发表时间：
2019-03-04
期刊：
影响因子：
7.7
通讯作者：
Grubmueller, Helmut
中科院分区：
文献类型：
--
作者：
Igaev, Maxim;Kutzner, Carsten;Grubmueller, Helmut
我们提出了一种相关驱动的分子动力学（CDMD）方法，用于在从近原子到亚纳米的分辨率范围内将原子模型自动细化到低温电子显微镜（cryo-EM）图。它利用化学精确力场和热力学采样来提高模型结构与低温电镜图之间的实空间相关性。我们的框架采用逐步提高分辨率和地图模型一致性以及模拟退火，并允许完全自动化的改进，无需人工干预或任何额外的转子和骨干特定限制。使用多个具有挑战性的系统，涵盖广泛的地图分辨率、系统大小、起始模型几何形状和距离目标状态的距离，我们从模型精度和过拟合的可能性两方面评估生成模型的质量。为了提供一个客观的比较，我们在所有的例子中应用了几种成熟的方法，并证明CDMD在大多数情况下表现最好。
We present a correlation-driven molecular dynamics (CDMD) method for automated refinement of atomistic models into cryo-electron microscopy (cryo-EM) maps at resolutions ranging from near-atomic to subnanometer. It utilizes a chemically accurate force field and thermodynamic sampling to improve the real-space correlation between the modeled structure and the cryo-EM map. Our framework employs a gradual increase in resolution and map-model agreement as well as simulated annealing, and allows fully automated refinement without manual intervention or any additional rotamer-and backbone-specific restraints. Using multiple challenging systems covering a wide range of map resolutions, system sizes, starting model geometries and distances from the target state, we assess the quality of generated models in terms of both model accuracy and potential of overfitting. To provide an objective comparison, we apply several wellestablished methods across all examples and demonstrate that CDMD performs best in most cases.