Improving the accuracy of NMR structures of RNA by means of conformational database potentials of mean force as assessed by complete dipolar coupling cross-validation

J Am Chem Soc. 2003 Feb 12;125(6):1518-25. doi: 10.1021/ja028383j.

Abstract

The description of the nonbonded contact terms used in simulated annealing refinement can have a major impact on nucleic acid structures generated from NMR data. Using complete dipolar coupling cross-validation, we demonstrate that substantial improvements in coordinate accuracy of NMR structures of RNA can be obtained by making use of two conformational database potentials of mean force: a nucleic acid torsion angle database potential consisting of various multidimensional torsion angle correlations; and an RNA specific base-base positioning potential that provides a simple geometric, statistically based, description of sequential and nonsequential base-base interactions. The former is based on 416 nucleic acid crystal structures solved at a resolution of </=2 A and an R-factor </=25%; the latter is based on 131 RNA crystal structures solved at a resolution of </=3 A and an R-factor of </=25%, and includes both the large and small subunits of the ribosome. The application of these two database potentials is illustrated for the structure refinement of an RNA aptamer/theophylline complex for which extensive NOE and residual dipolar coupling data have been measured in solution.

Publication types

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

MeSH terms

  • Databases, Nucleic Acid
  • Models, Molecular
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Nucleic Acid Conformation
  • RNA / chemistry*
  • Reproducibility of Results
  • Static Electricity
  • Theophylline / chemistry

Substances

  • RNA
  • Theophylline

Associated data

  • PDB/1O15