National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R21-AI137696
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P01-AI095208
米国
National Science Foundation (NSF, United States)
1902392
米国
Welch Foundation
1863
米国
引用
ジャーナル: RNA / 年: 2020 タイトル: Hierarchical natural move Monte Carlo refines flexible RNA structures into cryo-EM densities. 著者: Jeng-Yih Chang / Zhicheng Cui / Kailu Yang / Jianhua Huang / Peter Minary / Junjie Zhang / 要旨: Ribonucleic acids (RNAs) play essential roles in living cells. Many of them fold into defined three-dimensional (3D) structures to perform functions. Recent advances in single-particle cryo-electron ...Ribonucleic acids (RNAs) play essential roles in living cells. Many of them fold into defined three-dimensional (3D) structures to perform functions. Recent advances in single-particle cryo-electron microscopy (cryo-EM) have enabled structure determinations of RNA to atomic resolutions. However, most RNA molecules are structurally flexible, limiting the resolution of their structures solved by cryo-EM. In modeling these molecules, several computational methods are limited by the requirement of massive computational resources and/or the low efficiency in exploring large-scale structural variations. Here we use hierarchical natural move Monte Carlo (HNMMC), which takes advantage of collective motions for groups of nucleic acid residues, to refine RNA structures into their cryo-EM maps, preserving atomic details in the models. After validating the method on a simulated density map of tRNA, we applied it to objectively obtain the model of the folding intermediate for the specificity domain of ribonuclease P from and refine a flexible ribosomal RNA (rRNA) expansion segment from the () ribosome in different conformational states. Finally, we used HNMMC to model atomic details and flexibility for two distinct conformations of the complete genomic RNA (gRNA) inside MS2, a single-stranded RNA virus, revealing multiple pathways for its capsid assembly.