Three-dimensional RNA structure refinement by hydroxyl radical probing

Feng Ding, Christopher A. Lavender, Kevin M. Weeks, Nikolay Dokholyan

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Molecular modeling guided by experimentally derived structural information is an attractive approach for three-dimensional structure determination of complex RNAs that are not amenable to study by high-resolution methods. Hydroxyl radical probing (HRP), which is performed routinely in many laboratories, provides a measure of solvent accessibility at individual nucleotides. HRP measurements have, to date, only been used to evaluate RNA models qualitatively. Here we report the development of a quantitative structure refinement approach using HRP measurements to drive discrete molecular dynamics simulations for RNAs ranging in size from 80 to 230 nucleotides. We first used HRP reactivities to identify RNAs that form extensive helical packing interactions. For these RNAs, we achieved highly significant structure predictions given the inputs of RNA sequence and base pairing. This HRP-directed tertiary structure refinement approach generates robust structural hypotheses that are useful for guiding explorations of structure-function inter-relationships in RNA.

Original languageEnglish (US)
Pages (from-to)603-608
Number of pages6
JournalNature methods
Volume9
Issue number6
DOIs
StatePublished - Jun 2012

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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