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 journalArticle

8 Citations (Scopus)

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

Fingerprint

Hydroxyl Radical
RNA
Guide RNA
Tetrahymena
Molecular Dynamics Simulation
Introns
Molecular dynamics
Nucleotides
octogen
Computer simulation
Experiments

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Homan, P. J., Tandon, A., Rice, G. M., Ding, F., Dokholyan, N. V., & Weeks, K. M. (2014). RNA tertiary structure analysis by 2?-Hydroxyl molecular interference. Biochemistry, 53(43), 6825-6833. https://doi.org/10.1021/bi501218g
Homan, Philip J. ; Tandon, Arpit ; Rice, Greggory M. ; Ding, Feng ; Dokholyan, Nikolay V. ; Weeks, Kevin M. / RNA tertiary structure analysis by 2?-Hydroxyl molecular interference. In: Biochemistry. 2014 ; Vol. 53, No. 43. pp. 6825-6833.
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Homan, PJ, Tandon, A, Rice, GM, Ding, F, Dokholyan, NV & Weeks, KM 2014, 'RNA tertiary structure analysis by 2?-Hydroxyl molecular interference', Biochemistry, vol. 53, no. 43, pp. 6825-6833. https://doi.org/10.1021/bi501218g

RNA tertiary structure analysis by 2?-Hydroxyl molecular interference. / Homan, Philip J.; Tandon, Arpit; Rice, Greggory M.; Ding, Feng; Dokholyan, Nikolay V.; Weeks, Kevin M.

In: Biochemistry, Vol. 53, No. 43, 04.11.2014, p. 6825-6833.

Research output: Contribution to journalArticle

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