Three-dimensional RNA structure refinement by hydroxyl radical probing

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

Research output: Contribution to journalArticle

53 Citations (Scopus)

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 1 2012

Fingerprint

Hydroxyl Radical
RNA
Nucleotides
Molecular Dynamics Simulation
Molecular modeling
Base Pairing
Molecular dynamics
Computer simulation

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ding, Feng ; Lavender, Christopher A. ; Weeks, Kevin M. ; Dokholyan, Nikolay. / Three-dimensional RNA structure refinement by hydroxyl radical probing. In: Nature methods. 2012 ; Vol. 9, No. 6. pp. 603-608.
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Three-dimensional RNA structure refinement by hydroxyl radical probing. / Ding, Feng; Lavender, Christopher A.; Weeks, Kevin M.; Dokholyan, Nikolay.

In: Nature methods, Vol. 9, No. 6, 01.06.2012, p. 603-608.

Research output: Contribution to journalArticle

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