title: Probability assessment of conformational ensembles: sugar repuckering in a DNA duplex in solution.
abstract: Conformational flexibility of molecules in solution implies that different conformers contribute to the NMR signal. This may lead to internal inconsistencies in the 2D NOE-derived interproton distance restraints and to conflict with scalar coupling-based torsion angle restraints. Such inconsistencies have been revealed and analyzed for the DNA octamer GTATAATG.CATATTAC, containing the Pribnow box consensus sequence. A number of subsets of distance restraints were constructed and used in the restrained Monte Carlo refinement of different double-helical conformers. The probabilities of conformers were then calculated by a quadratic programming algorithm, minimizing a relaxation rate-base residual index. The calculated distribution of conformers agrees with the experimental NOE data as an ensemble better than any single structure. A comparison with the results of this procedure, which we term PARSE (Probability Assessment via Relaxation rates of a Structural Ensemble), to an alternative method to generate solution ensembles showed, however, that the detailed multi-conformational description of solution DNA structure remains ambiguous at this stage. Nevertheless, some ensemble properties can be deduced with confidence, the most prominent being a distribution of sugar puckers with minor populations in the N-region and major populations in the S-region. Importantly, such a distribution is in accord with the analysis of independent experimental data--deoxyribose proton-proton scalar coupling constants.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco 94143-0446.
authors.forename: N B
authors.initials: NB
authors.lastname: Ulyanov
authors.forename: U
authors.initials: U
authors.lastname: Schmitz
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: T L
authors.initials: TL
authors.lastname: James
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D055592:Biophysical Phenomena; D001703:Biophysics; D002241:Carbohydrates / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009010:Monte Carlo Method; D009690:Nucleic Acid Conformation; D011336:Probability; D011522:Protons; D012996:Solutions; D013816:Thermodynamics
chemical_list: D002241:Carbohydrates; D011522:Protons; D012996:Solutions; D004247:DNA