RNA tertiary structure analysis by 2?-Hydroxyl molecular interference

Philip J. Homan, Arpit Tandon, Greggory M. Rice, Feng Ding, Nikolay V. Dokholyan, Kevin M. Weeks

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

We introduce a melded chemical and computational approach for probing and modeling higher-order intramolecular tertiary interactions in RNA. 2?- molecular interference (HMX) identifies nucleotides in highly packed regions of an RNA by exploiting the ability of bulky adducts at the 2?-hydroxyl position to disrupt overall RNA structure. HMX was found to be exceptionally selective for quantitative detection of higher-order and tertiary interactions. When incorporated as experimental constraints in discrete molecular dynamics simulations, HMX information yielded accurate three-dimensional models, emphasizing the power of molecular interference to guide RNA tertiary structure analysis and fold refinement. In the case of a large, multidomain RNA, the Tetrahymena group I intron, HMX identified multiple distinct sets of tertiary structure interaction groups in a single, concise experiment.

Original languageEnglish (US)
Pages (from-to)6825-6833
Number of pages9
JournalBiochemistry
Volume53
Issue number43
DOIs
StatePublished - Nov 4 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry

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