title: Nuclear Magnetic Resonance-Assisted Prediction of Secondary Structure for RNA: Incorporation of Direction-Dependent Chemical Shift Constraints.
abstract: Knowledge of RNA structure is necessary to determine structure-function relationships and to facilitate design of potential therapeutics. RNA secondary structure prediction can be improved by applying constraints from nuclear magnetic resonance (NMR) experiments to a dynamic programming algorithm. Imino proton walks from NOESY spectra reveal double-stranded regions. Chemical shifts of protons in GH1, UH3, and UH5 of GU pairs, UH3, UH5, and AH2 of AU pairs, and GH1 of GC pairs were analyzed to identify constraints for the 5' to 3' directionality of base pairs in helices. The 5' to 3' directionality constraints were incorporated into an NMR-assisted prediction of secondary structure (NAPSS-CS) program. When it was tested on 18 structures, including nine pseudoknots, the sensitivity and positive predictive value were improved relative to those of three unrestrained programs. The prediction accuracy for the pseudoknots improved the most. The program also facilitates assignment of chemical shifts to individual nucleotides, a necessary step for determining three-dimensional structure.
authors.affiliation: Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry , Rochester, New York 14642, United States.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Bellaousov
authors.affiliation: Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Tubbs
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry , Rochester, New York 14642, United States.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kennedy
authors.affiliation: Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lopez
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry , Rochester, New York 14642, United States.|Center for RNA Biology, University of Rochester , Rochester, New York 14642, United States.
authors.forename: David H
authors.initials: DH
authors.lastname: Mathews
authors.affiliation: Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.|Center for RNA Biology, University of Rochester , Rochester, New York 14642, United States.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Turner
mesh_terms: D000465:Algorithms; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D008979:Moloney murine leukemia virus / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D009690:Nucleic Acid Conformation; D011237:Predictive Value of Tests; D011522:Protons; D012313:RNA / Q000737:chemistry*; D012367:RNA, Viral / Q000737:chemistry; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
chemical_list: D011522:Protons; D012367:RNA, Viral; D012313:RNA