Book of Abstracts: Albany 2005

category image Volume 22
No. 6
June 2005

Principles of RNA Base Pairing: Structures and Energies of Cis and Trans-Watson-Crick/Sugar Edge Base Pairs Revealed by Quantum Chemical Calculations

Due to the presence of 2'-OH hydroxyl group of ribose, RNA molecules utilize an astonishing variability of base pairing patterns to build up their structures and perform the biological functions. Many of the key RNA base-pairing families have no counterparts in DNA. In this study, the cis-Watson-Crick/Sugar Edge (cis-WC/SE) and trans-Watson-Crick/Sugar Edge (trans-WC/SE) RNA base pair families have been characterized using quantum chemical and molecular mechanics calculations. These two families may form up to 32 unique base pairing patterns. Gas-phase optimized geometries from DFT calculations and RIMP2 interaction energies are reported for the 10 crystallographically identified trans-WC/SE and 13 cis-WC/SE base pairing patterns. Further, stable structures are predicted for all remaining 9 possible members of these families not seen in RNAs so far. Among these novel 9 base pairs, the computations substantially refine several structures suggested earlier based on simple isosteric considerations. Plausible structures are also predicted for pairs where no arrangement was suggested before. Thus our study brings a complete set of 32 cis and trans-WC/SE base pairing patterns. Their computed steric sizes (lengths) are in a sound correlation with the x-ray data. This confirms that isostericity of RNA base pairs, which is one of the key factors determining the RNA sequence conservation patterns, originates in properties of the isolated base pairs. In contrast to the cis-structures, the isosteric subgroups of the trans-WC/SE family vary not only in their H-bonding patterns and steric dimensions, but also in the intrinsic strength of the intermolecular interactions. The present quantum-chemical calculations for the first time analyze base pairs involving the ribose 2'-OH group and unambiguously correlate the structural information known from experiments with the energetics of interactions. Statistical analysis of the interaction energy terms over all WC/SE base pairs reveals that distribution of the total interaction energy over the sugar-base and base-base contributions is controlled by the cis-trans isomerism. Good performance of the AMBER force field is noticed.

References and Footnotes
  1. J. E. Sponer, N. Spackova, P. Kulhanek, J. Leszczynski, and J. Sponer. J. Phys. Chem. A, in press.

Judit E. Sponer1,*
Jerzy Leszczynski2
Jiri Sponer1,3,*

1Institute of Biophysics
Academy of Sciences of the Czech Republic
Kralovopolska 135
612 65 Brno, Czech Republic
2Department of Chemistry
Computational Center for Molecular Structure and Interactions
Jackson State University
Jackson, Mississippi 39217, USA
3Institute of Organic Chemistry and Biochemistry
Academy of Sciences of the Czech Republic
Flemingovo namesti 2
166 10 Prague 6, Czech Republic

*Corresponding authors:
Fax: 420 5412 12179