华中科技大学黄胜友等研究人员合作实现根据冷冻电镜图谱确定全原子RNA结构。这一研究成果于2024年2月23日在线发表在国际学术期刊《自然—生物技术》上。

研究人员开发了EMRNA，这是一种从冷冻电镜图谱中准确、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、考虑序列和二级结构信息的评分以及RNA结构的全原子构建。研究人员在分辨率为2.0-6.0 Å、长度从37nt到423nt的140个不同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的中位精确度为2.36 Å均方根偏差和0.86 TM-score，而auto-DRRAFTER为6.66 Å和0.58。在构建的模型中，EMRNA还获得了较高的残基覆盖率和序列匹配率，分别为93.30%和95.30%，而phenix.map_too_model为58.20%和42.20%，CryoREAD为56.45%和52.3%。EMRNA的速度很快，能在3分钟内构建100 nt的RNA结构。

研究人员表示，从冷冻电镜图谱中确定蛋白质结构的方法很多，但对于RNA结构来说，这仍然是一项挑战。

附：英文原文

Title: All-atom RNA structure determination from cryo-EM maps

Author: Li, Tao, He, Jiahua, Cao, Hong, Zhang, Yi, Chen, Ji, Xiao, Yi, Huang, Sheng-You

Issue&Volume: 2024-02-23

Abstract: 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 423nt at 2.0–6.0 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 root mean square deviation and 0.86 TM-score for full-length RNA structures, compared with 6.66 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 100nt within 3min.

DOI: 10.1038/s41587-024-02149-8

Source: https://www.nature.com/articles/s41587-024-02149-8