Structure modeling of RNA using sparse NMR constraints

Benfeard Williams, Bo Zhao, Arpit Tandon, Feng Ding, Kevin M. Weeks, Qi Zhang, Nikolay V. Dokholyan

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

RNAs fold into distinct molecular conformations that are often essential for their functions. Accurate structure modeling of complex RNA motifs, including ubiquitous non-canonical base pairs and pseudoknots, remains a challenge. Here, we present an NMR-guided all-atom discrete molecular dynamics (DMD) platform, iFoldNMR, for rapid and accurate structure modeling of complex RNAs. We show that sparse distance constraints from imino resonances, which can be readily obtained from routine NMR experiments and easier to compile than laborious assignments of non-solvent-exchangeable protons, are sufficient to direct a DMD search for low-energy RNA conformers. Benchmarking on a set of RNAs with complex folds spanning up to 56 nucleotides in length yields structural models that recapitulate experimentally determined structures with all-heavy atom RMSDs ranging from 2.4 to 6.5 Å. This platform represents an efficient approach for high-throughput RNA structuremodeling and will facilitate analysis of diverse, newly discovered functional RNAs.

Original languageEnglish (US)
Pages (from-to)12638-12647
Number of pages10
JournalNucleic acids research
Volume45
Issue number22
DOIs
StatePublished - Dec 15 2017

All Science Journal Classification (ASJC) codes

  • Genetics

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