Suppr超能文献

从冷冻电镜图谱中快速且自动化地构建蛋白质-DNA/RNA 大分子复合物模型。

Fast and automated protein-DNA/RNA macromolecular complex modeling from cryo-EM maps.

机构信息

Division of Computing and Software Systems, University of Washington Bothell, Bothell, WA 98011, USA.

Department of Computer Science, Duke University, Durham, NC 27708, USA.

出版信息

Brief Bioinform. 2023 Mar 19;24(2). doi: 10.1093/bib/bbac632.

Abstract

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/.

摘要

低温电子显微镜(cryo-EM)可以在三维库仑势图中重建蛋白质-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分子机制提供了基础,包括许多人类疾病。然而,大型大分子复合物的模型构建通常具有难度和耗时的特点。我们最近开发了基于人工智能的 DeepTracer-2.0 流水线,可以从单个低温电子显微镜图中构建氨基酸和核酸骨架,甚至根据侧链密度预测最佳拟合残基。在对蛋白质-DNA/RNA 复合物的独立实验图谱进行基准测试时,该实验显示出了改进的准确性和效率,并展示了从低温电子显微镜图谱进行大分子建模的广阔前景。我们的方法和流水线可以使从事分子生物医学和药物发现的全球研究人员受益,并极大地提高低温电子显微镜模型构建的通量。该流水线已整合到网页门户 https://deeptracer.uw.edu/ 中。

相似文献

1
Fast and automated protein-DNA/RNA macromolecular complex modeling from cryo-EM maps.
Brief Bioinform. 2023 Mar 19;24(2). doi: 10.1093/bib/bbac632.
2
Smart de novo Macromolecular Structure Modeling from Cryo-EM Maps.
J Mol Biol. 2023 May 1;435(9):167967. doi: 10.1016/j.jmb.2023.167967. Epub 2023 Jan 18.
3
DeepTracer for fast de novo cryo-EM protein structure modeling and special studies on CoV-related complexes.
Proc Natl Acad Sci U S A. 2021 Jan 12;118(2). doi: 10.1073/pnas.2017525118.
4
Current approaches for the fitting and refinement of atomic models into cryo-EM maps using CCP-EM.
Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):492-505. doi: 10.1107/S2059798318007313. Epub 2018 May 30.
5
Predictive modeling and cryo-EM: A synergistic approach to modeling macromolecular structure.
Biophys J. 2024 Feb 20;123(4):435-450. doi: 10.1016/j.bpj.2024.01.021. Epub 2024 Jan 23.
6
The accuracy of protein models automatically built into cryo-EM maps with ARP/wARP.
Acta Crystallogr D Struct Biol. 2021 Feb 1;77(Pt 2):142-150. doi: 10.1107/S2059798320016332. Epub 2021 Jan 26.
7
DeepTracer-ID: De novo protein identification from cryo-EM maps.
Biophys J. 2022 Aug 2;121(15):2840-2848. doi: 10.1016/j.bpj.2022.06.025. Epub 2022 Jun 28.
8
CryoREAD: de novo structure modeling for nucleic acids in cryo-EM maps using deep learning.
Nat Methods. 2023 Nov;20(11):1739-1747. doi: 10.1038/s41592-023-02032-5. Epub 2023 Oct 2.
9
Automated Modeling and Validation of Protein Complexes in Cryo-EM Maps.
Methods Mol Biol. 2021;2215:189-223. doi: 10.1007/978-1-0716-0966-8_9.

引用本文的文献

3
Advancing structure modeling from cryo-EM maps with deep learning.
Biochem Soc Trans. 2025 Feb 7;53(1):BST20240784. doi: 10.1042/BST20240784.
4
RNA sample optimization for cryo-EM analysis.
Nat Protoc. 2025 May;20(5):1114-1157. doi: 10.1038/s41596-024-01072-1. Epub 2024 Nov 15.
5
Automated detection and de novo structure modeling of nucleic acids from cryo-EM maps.
Nat Commun. 2024 Oct 30;15(1):9367. doi: 10.1038/s41467-024-53721-4.
6
Automated model building and protein identification in cryo-EM maps.
Nature. 2024 Apr;628(8007):450-457. doi: 10.1038/s41586-024-07215-4. Epub 2024 Feb 26.
7
All-atom RNA structure determination from cryo-EM maps.
Nat Biotechnol. 2025 Jan;43(1):97-105. doi: 10.1038/s41587-024-02149-8. Epub 2024 Feb 23.
8

本文引用的文献

1
Deep learning for reconstructing protein structures from cryo-EM density maps: Recent advances and future directions.
Curr Opin Struct Biol. 2023 Apr;79:102536. doi: 10.1016/j.sbi.2023.102536. Epub 2023 Feb 9.
3
CR-I-TASSER: assemble protein structures from cryo-EM density maps using deep convolutional neural networks.
Nat Methods. 2022 Feb;19(2):195-204. doi: 10.1038/s41592-021-01389-9. Epub 2022 Feb 7.
4
Mechanism of siRNA production by a plant Dicer-RNA complex in dicing-competent conformation.
Science. 2021 Nov 26;374(6571):1152-1157. doi: 10.1126/science.abl4546. Epub 2021 Oct 14.
5
Structures and implications of TBP-nucleosome complexes.
Proc Natl Acad Sci U S A. 2021 Jul 27;118(30). doi: 10.1073/pnas.2108859118.
7
Cryo-EM model validation recommendations based on outcomes of the 2019 EMDataResource challenge.
Nat Methods. 2021 Feb;18(2):156-164. doi: 10.1038/s41592-020-01051-w. Epub 2021 Feb 4.
8
DeepTracer for fast de novo cryo-EM protein structure modeling and special studies on CoV-related complexes.
Proc Natl Acad Sci U S A. 2021 Jan 12;118(2). doi: 10.1073/pnas.2017525118.
9
FARFAR2: Improved De Novo Rosetta Prediction of Complex Global RNA Folds.
Structure. 2020 Aug 4;28(8):963-976.e6. doi: 10.1016/j.str.2020.05.011. Epub 2020 Jun 11.
10
Haruspex: A Neural Network for the Automatic Identification of Oligonucleotides and Protein Secondary Structure in Cryo-Electron Microscopy Maps.
Angew Chem Int Ed Engl. 2020 Aug 24;59(35):14788-14795. doi: 10.1002/anie.202000421. Epub 2020 May 11.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验