Division of Computing and Software Systems, University of Washington Bothell, Bothell, WA 98011.
Division of Computing and Software Systems, University of Washington Bothell, Bothell, WA 98011
Proc Natl Acad Sci U S A. 2021 Jan 12;118(2). doi: 10.1073/pnas.2017525118.
Information about macromolecular structure of protein complexes and related cellular and molecular mechanisms can assist the search for vaccines and drug development processes. To obtain such structural information, we present DeepTracer, a fully automated deep learning-based method for fast de novo multichain protein complex structure determination from high-resolution cryoelectron microscopy (cryo-EM) maps. We applied DeepTracer on a previously published set of 476 raw experimental cryo-EM maps and compared the results with a current state of the art method. The residue coverage increased by over 30% using DeepTracer, and the rmsd value improved from 1.29 Å to 1.18 Å. Additionally, we applied DeepTracer on a set of 62 coronavirus-related cryo-EM maps, among them 10 with no deposited structure available in EMDataResource. We observed an average residue match of 84% with the deposited structures and an average rmsd of 0.93 Å. Additional tests with related methods further exemplify DeepTracer's competitive accuracy and efficiency of structure modeling. DeepTracer allows for exceptionally fast computations, making it possible to trace around 60,000 residues in 350 chains within only 2 h. The web service is globally accessible at https://deeptracer.uw.edu.
有关蛋白质复合物的大分子结构以及相关的细胞和分子机制的信息可以帮助寻找疫苗和药物开发过程。为了获得这种结构信息，我们提出了 DeepTracer，这是一种基于深度学习的全自动方法，可从高分辨率冷冻电镜 (cryo-EM) 图谱中快速从头确定多链蛋白质复合物结构。我们将 DeepTracer 应用于之前发表的 476 组原始实验 cryo-EM 图谱，并将结果与当前最先进的方法进行了比较。使用 DeepTracer 后，残基覆盖率增加了 30%以上，rmsd 值从 1.29 Å 提高到了 1.18 Å。此外，我们还将 DeepTracer 应用于一组 62 个与冠状病毒相关的 cryo-EM 图谱，其中 10 个图谱在 EMDataResource 中没有可用的已发表结构。我们观察到与已发表结构的平均残基匹配度为 84%，平均 rmsd 为 0.93 Å。与相关方法的进一步测试进一步证明了 DeepTracer 在结构建模方面的准确性和效率具有竞争力。DeepTracer 允许进行非常快速的计算，仅在 2 小时内就可以追踪大约 60,000 个残基和 350 条链。该网络服务可在 https://deeptracer.uw.edu 上全球访问。
