Li Tao, He Jiahua, Cao Hong, Zhang Yi, Chen Ji, Xiao Yi, Huang Sheng-You
School of Physics and Key Laboratory of Molecular Biophysics of MOE, Huazhong University of Science and Technology, Wuhan, China.
Nat Biotechnol. 2025 Jan;43(1):97-105. doi: 10.1038/s41587-024-02149-8. Epub 2024 Feb 23.
Many methods exist for determining protein structures from cryogenic electron microscopy maps, but this remains challenging for RNA structures. Here we developed EMRNA, a method for accurate, automated determination of full-length all-atom RNA structures from cryogenic electron microscopy maps. EMRNA integrates deep learning-based detection of nucleotides, three-dimensional backbone tracing and scoring with consideration of sequence and secondary structure information, and full-atom construction of the RNA structure. We validated EMRNA on 140 diverse RNA maps ranging from 37 to 423 nt at 2.0-6.0 Å resolutions, and compared EMRNA with auto-DRRAFTER, phenix.map_to_model and CryoREAD on a set of 71 cases. EMRNA achieves a median accuracy of 2.36 Å root mean square deviation and 0.86 TM-score for full-length RNA structures, compared with 6.66 Å and 0.58 for auto-DRRAFTER. EMRNA also obtains a high residue coverage and sequence match of 93.30% and 95.30% in the built models, compared with 58.20% and 42.20% for phenix.map_to_model and 56.45% and 52.3% for CryoREAD. EMRNA is fast and can build an RNA structure of 100 nt within 3 min.
存在多种从低温电子显微镜图谱确定蛋白质结构的方法,但对于RNA结构而言,这仍然具有挑战性。在此,我们开发了EMRNA,一种从低温电子显微镜图谱准确、自动确定全长全原子RNA结构的方法。EMRNA整合了基于深度学习的核苷酸检测、三维骨架追踪以及结合序列和二级结构信息的评分,以及RNA结构的全原子构建。我们在140个分辨率为2.0 - 6.0 Å、长度从37到423 nt的不同RNA图谱上验证了EMRNA,并在一组71个案例中将EMRNA与auto-DRRAFTER、phenix.map_to_model和CryoREAD进行了比较。对于全长RNA结构,EMRNA实现了2.36 Å的均方根偏差中位数和0.86的TM分数,而auto-DRRAFTER分别为6.66 Å和0.58。在构建的模型中,EMRNA还获得了93.30%和95.30%的高残基覆盖率和序列匹配率,相比之下,phenix.map_to_model分别为58.20%和42.20%,CryoREAD分别为56.45%和52.3%。EMRNA速度很快,能够在3分钟内构建一个100 nt的RNA结构。