title: A physical picture of atomic motions within the Dickerson DNA dodecamer in solution derived from joint ensemble refinement against NMR and large-angle X-ray scattering data.
abstract: The structure and dynamics of the Dickerson DNA dodecamer [5'd(CGCGAATTCGCG)2] in solution have been investigated by joint simulated annealing refinement against NMR and large-angle X-ray scattering data (extending from 0.25 to 3 A-1). The NMR data comprise an extensive set of hetero- and homonuclear residual dipolar coupling and 31P chemical shift anisotropy restraints in two alignment media, supplemented by NOE and 3J coupling data. The NMR and X-ray scattering data cannot be fully ascribed to a single structure representation, indicating the presence of anisotropic motions that impact the experimental observables in different ways. Refinement with ensemble sizes (Ne) of >or=2 to represent the atomic motions reconciles all the experimental data within measurement error. Cross validation against both the dipolar coupling and X-ray scattering data suggests that the optimal ensemble size required to account for the current data is 4. The resulting ensembles permit one to obtain a detailed view of the conformational space sampled by the dodecamer in solution and permit one to analyze fluctuations in helicoidal parameters, sugar puckers, and BI-BII backbone transitions and to obtain quantitative metrics of atomic motion such as generalized order parameters and thermal B factors. The calculated order parameters are in good agreement with experimental order parameters obtained from 13C relaxation measurements. Although DNA behaves as a relatively rigid rod with a persistence length of approximately 150 bp, dynamic conformational heterogeneity at the base pair level is functionally important since it readily permits optimization of intermolecular protein-DNA interactions.
authors.affiliation: Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Building 12A, Bethesda, Maryland 20892-5624, USA. charles.schwieters@nih.gov
authors.forename: Charles D
authors.initials: CD
authors.lastname: Schwieters
authors.forename: G Marius
authors.initials: GM
authors.lastname: Clore
mesh_terms: D020029:Base Pairing; D002236:Carbohydrate Conformation; D009682:Magnetic Resonance Spectroscopy; D009038:Motion; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D012996:Solutions; D014961:X-Ray Diffraction
chemical_list: D009838:Oligodeoxyribonucleotides; D012996:Solutions