title: RNA tertiary structure analysis by 2'-hydroxyl molecular interference.
abstract: We introduce a melded chemical and computational approach for probing and modeling higher-order intramolecular tertiary interactions in RNA. 2'-Hydroxyl 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.
authors.affiliation: Departments of Chemistry and ‡Biochemistry and Biophysics, University of North Carolina , Chapel Hill, North Carolina 27599-3290, United States.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Homan
authors.forename: Arpit
authors.initials: A
authors.lastname: Tandon
authors.forename: Greggory M
authors.initials: GM
authors.lastname: Rice
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Dokholyan
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Weeks
mesh_terms: D001412:Bacillus subtilis / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D012329:RNA, Bacterial / Q000737:chemistry*; D016053:RNA, Protozoan / Q000737:chemistry*; D013768:Tetrahymena / Q000737:chemistry*
chemical_list: D012329:RNA, Bacterial; D016053:RNA, Protozoan