Fast approximate methods for calculating nucleic acid base pair interaction energies

Journal of Computational Chemistry  vol. 24  p. 57-67  DOI: 10.1002/jcc.10150
PMID/PMCID: 12483675 Published: 2003-01-15 

Edward C. Sherer, Darrin M. York [ ] , Christopher J. Cramer

  View Full Article
 Download PDF


Interaction enthalpies for six base pairs have been computed at a variety of efficient levels of electronic structure theory and compared to experiment. In addition to previously defined levels of theory, modified Hamiltonians with adjusted parameters in hybrid Hartree–Fock/density functionals and semiempirical neglect-of-diatomic-differential-overlap models were examined. Of the pure and hybrid density functional levels, mPWPW91/MIDI! performed most satisfactorily, as judged by comparison not only to the available experimental data, but also to data from more robust electronic structure methods for 22 additional base pairs. The low computational cost of the mPWPW91/MIDI! model was further exploited in an investigation of various base trimers, tetramers, and one base pentamer. A carefully reparameterized semiempirical model, PM3BP, was able to achieve similar levels of accuracy at a still greater savings in terms of computational effort.