title: Stacking in RNA: NMR of Four Tetramers Benchmark Molecular Dynamics.
abstract: Molecular dynamics (MD) simulations for RNA tetramers r(AAAA), r(CAAU), r(GACC), and r(UUUU) are benchmarked against1H-1H NOESY distances and3Jscalar couplings to test effects of RNA torsion parametrizations. Four different starting structures were used for r(AAAA), r(CAAU), and r(GACC), while five starting structures were used for r(UUUU). On the basis of X-ray structures, criteria are reported for quantifying stacking. The force fields, AMBER ff99, parmbsc0, parm99χ_Yil, ff10, and parmTor, all predict experimentally unobserved stacks and intercalations, e.g., base 1 stacked between bases 3 and 4, and incorrect χ, ϵ, and sugar pucker populations. The intercalated structures are particularly stable, often lasting several microseconds. Parmbsc0, parm99χ_Yil, and ff10 give similar agreement with NMR, but the best agreement is only 46%. Experimentally unobserved intercalations typically are associated with reduced solvent accessible surface area along with amino and hydroxyl hydrogen bonds to phosphate nonbridging oxygens. Results from an extensive set of MD simulations suggest that recent force field parametrizations improve predictions, but further improvements are necessary to provide reasonable agreement with NMR. In particular, intramolecular stacking and hydrogen bonding interactions may not be well balanced with the TIP3P water model. NMR data and the scoring method presented here provide rigorous benchmarks for future changes in force fields and MD methods.
authors.affiliation: Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Condon
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester , Rochester, New York 14642, United States.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kennedy
authors.affiliation: University of Rochester Center for Integrated Research Computing , Rochester, New York 14627, United States.
authors.forename: Brendan C
authors.initials: BC
authors.lastname: Mort
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences , 60-704 Poznan, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Kierzek
authors.affiliation: Department of Chemistry, University of Rochester , Rochester, New York 14627, United States ; Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Ilyas
authors.initials: I
authors.lastname: Yildirim
authors.affiliation: Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Turner