PT  - JOURNAL ARTICLE
AU  - Kalli Kappel
AU  - Kaiming Zhang
AU  - Zhaoming Su
AU  - Wipapat Kladwang
AU  - Shanshan Li
AU  - Grigore Pintilie
AU  - Ved V. Topkar
AU  - Ramya Rangan
AU  - Ivan N. Zheludev
AU  - Andrew M. Watkins
AU  - Joseph D. Yesselman
AU  - Wah Chiu
AU  - Rhiju Das
TI  - Ribosolve: Rapid determination of three-dimensional RNA-only structures
AID  - 10.1101/717801
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 717801
4099  - http://biorxiv.org/content/early/2019/07/31/717801.short
4100  - http://biorxiv.org/content/early/2019/07/31/717801.full
AB  - The discovery and design of biologically important RNA molecules is dramatically outpacing three-dimensional structural characterization. To address this challenge, we present Ribosolve, a hybrid method integrating moderate-resolution cryo-EM maps, chemical mapping, and Rosetta computational modeling, and demonstrate its application to thirteen previously unknown 119-to 338-nucleotide protein-free RNA-only structures: full-length Tetrahymena ribozyme, hc16 ligase with and without substrate, full-length V. cholerae and F. nucleatum glycine riboswitch aptamers with and without glycine, Mycobacterium SAM-IV riboswitch with and without S-adenosylmethionine, and computer-designed spinach-TTR-3, eterna3D-JR_1, and ATP-TTR-3 with and without AMP. Blind challenges, prospective compensatory mutagenesis, internal controls, and simulation benchmarks validate the Ribosolve models and establish that modeling convergence is quantitatively predictive of model accuracy. These results demonstrate that RNA-only 3D structure determination can be rapid and routine.