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

Biochemistry. 2007 Feb 6;46(5):1152-66. doi: 10.1021/bi061943x.


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing
  • Carbohydrate Conformation
  • Magnetic Resonance Spectroscopy
  • Motion
  • Oligodeoxyribonucleotides / chemistry*
  • Solutions
  • X-Ray Diffraction


  • Oligodeoxyribonucleotides
  • Solutions