Fast and automated protein-DNA/RNA macromolecular complex modeling from cryo-EM maps.
Fast and automated protein-DNA/RNA macromolecular complex modeling from cryo-EM maps.
复制标题
根据冷冻电镜图进行快速、自动化的蛋白质-DNA/RNA 大分子复合物建模。
DOI：
10.1093/bib/bbac632
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发表时间：
2023
影响因子：
9.5
通讯作者：
Si,Dong
中科院分区：
文献类型：
--
作者：
Nakamura,Andrew;Meng,Hanze;Zhao,Minglei;Wang,Fengbin;Hou,Jie;Cao,Renzhi;Si,Dong
冷冻电子显微镜 (cryo-EM) 允许在三维库仑电位图中重建蛋白质-DNA/RNA 复合物等大分子结构。这些大分子复合物的结构信息为理解包括许多人类疾病在内的分子机制奠定了基础。然而，大分子复合物的模型构建通常是困难且耗时的。我们最近开发了 DeepTracer-2.0，这是一种基于人工智能的管道，可以从单个冷冻电镜图构建氨基酸和核酸主链，甚至可以根据侧链的密度预测最合适的残基。这些实验表明，在对蛋白质-DNA/RNA 复合物的独立实验图谱进行基准测试时，准确性和效率得到了提高，并证明了利用冷冻电镜图谱进行大分子建模的广阔前景。我们的方法和流程可以使全世界从事分子生物医学和药物发现的研究人员受益，并大幅提高冷冻电镜模型构建的吞吐量。该管道已集成到门户网站 https://deeptracer.uw.edu/ 中。
Cryo-electron microscopy (cryo-EM) allows a macromolecular structure such as protein-DNA/RNA complexes to be reconstructed in a three-dimensional coulomb potential map. The structural information of these macromolecular complexes forms the foundation for understanding the molecular mechanism including many human diseases. However, the model building of large macromolecular complexes is often difficult and time-consuming. We recently developed DeepTracer-2.0, an artificial-intelligence-based pipeline that can build amino acid and nucleic acid backbones from a single cryo-EM map, and even predict the best-fitting residues according to the density of side chains. The experiments showed improved accuracy and efficiency when benchmarking the performance on independent experimental maps of protein-DNA/RNA complexes and demonstrated the promising future of macromolecular modeling from cryo-EM maps. Our method and pipeline could benefit researchers worldwide who work in molecular biomedicine and drug discovery, and substantially increase the throughput of the cryo-EM model building. The pipeline has been integrated into the web portal https://deeptracer.uw.edu/.