title: Benchmarking AMBER force fields for RNA: comparisons to NMR spectra for single-stranded r(GACC) are improved by revised χ torsions.
abstract: Accurately modeling unpaired regions of RNA is important for predicting structure, dynamics, and thermodynamics of folded RNA. Comparisons between NMR data and molecular dynamics simulations provide a test of force fields used for modeling. Here, NMR spectroscopy, including NOESY, (1)H-(31)P HETCOR, DQF-COSY, and TOCSY, was used to determine conformational preferences for single-stranded GACC RNA. The spectra are consistent with a conformational ensemble containing major and minor A-form-like structures. In a series of 50 ns molecular dynamics (MD) simulations with the AMBER99 force field in explicit solvent, initial A-form-like structures rapidly evolve to disordered conformations. A set of 50 ns simulations with revised χ torsions (AMBER99χ force field) gives two primary conformations, consistent with the NMR spectra. A single 1.9 μs MD simulation with the AMBER99χ force field showed that the major and minor conformations are retained for almost 68% of the time in the first 700 ns, with multiple transformations from A-form to non-A-form conformations. For the rest of the simulation, random-coil structures and a stable non-A-form conformation inconsistent with NMR spectra were seen. Evidently, the AMBER99χ force field improves structural predictions for single-stranded GACC RNA compared to the AMBER99 force field, but further force field improvements are needed.
authors: Department of Chemistry, University of Rochester, Rochester, New York 14627, USA.
authors: Ilyas
authors: I
authors: Yildirim
authors: Harry A
authors: HA
authors: Stern
authors: Jason D
authors: JD
authors: Tubbs
authors: Scott D
authors: SD
authors: Kennedy
authors: Douglas H
authors: DH
authors: Turner
mesh_terms: D001483:Base Sequence; D019985:Benchmarking; D002241:Carbohydrates / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D002241:Carbohydrates; D012313:RNA