A new hydrogen-bonding potential for the design of protein-RNA interactions predicts specific contacts and discriminates decoys

Nucleic Acids Res. 2004 Sep 30;32(17):5147-62. doi: 10.1093/nar/gkh785. Print 2004.

Abstract

RNA-binding proteins play many essential roles in the regulation of gene expression in the cell. Despite the significant increase in the number of structures for RNA-protein complexes in the last few years, the molecular basis of specificity remains unclear even for the best-studied protein families. We have developed a distance and orientation-dependent hydrogen-bonding potential based on the statistical analysis of hydrogen-bonding geometries that are observed in high-resolution crystal structures of protein-DNA and protein-RNA complexes. We observe very strong geometrical preferences that reflect significant energetic constraints on the relative placement of hydrogen-bonding atom pairs at protein-nucleic acid interfaces. A scoring function based on the hydrogen-bonding potential discriminates native protein-RNA structures from incorrectly docked decoys with remarkable predictive power. By incorporating the new hydrogen-bonding potential into a physical model of protein-RNA interfaces with full atom representation, we were able to recover native amino acids at protein-RNA interfaces.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Computational Biology / methods*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Data Interpretation, Statistical
  • Databases, Protein
  • Hydrogen Bonding
  • Models, Molecular*
  • Molecular Structure
  • Protein Binding
  • RNA / chemistry
  • RNA / metabolism
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • RNA-Binding Proteins
  • RNA