Probability assessment of conformational ensembles: sugar repuckering in a DNA duplex in solution

Biophys J. 1995 Jan;68(1):13-24. doi: 10.1016/S0006-3495(95)80181-5.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Base Sequence
  • Biophysical Phenomena
  • Biophysics
  • Carbohydrates / chemistry
  • DNA / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Monte Carlo Method
  • Nucleic Acid Conformation*
  • Probability
  • Protons
  • Solutions
  • Thermodynamics

Substances

  • Carbohydrates
  • Protons
  • Solutions
  • DNA