Ab initio and density functional theory molecular orbital calculations have been performed for the four heterocyclic nucleic bases — adenine, thymine, guanine, and cytosine — in free and Watson-Crick hydrogen-bonded states using the Gaussian 98 suite of programs. Geometric optimizations and vibrational analyses were carried out by combinations of different methods and basis sets of increasing accuracy. The structures are optimized in stages of increasing computational intensity, starting with Hartree Fock self-consistent field calculations and successively followed by Becke-style three-parameter density functional theory (using the Lee-Yang-Parr correlation functional) and second-order Møller-Plesset perturbation theory. Preliminary computations reveal interesting features in the nucleic acid bases and hydrogen bonding complexes. Notably, the partial charges on the base-pair atoms differ significantly from those on the free bases. The differences occur primarily at the Watson-Crick hydrogen bonding sites and are more pronounced for G·C than A·T. Other atomic sites on the base pairs show significant accumulation of partial charge. The direction and magnitude of the dipole moments of the A·T and G·C complexes also differ significantly. In addition, the optimization of Watson-Crick interactions generates a propellering of base-pair planes of the same handedness found in high-resolution structures and heretofore attributed to stacking interactions between aromatic side groups. The low frequency normal modes of the energy-minimized base pairs also match sequence-dependent deformational tendencies observed in ensembles of crystal structures. (Supported by the U.S. Public Health Service research grant GM20861 to WKO and the National Science Foundation Advance Fellows Award 0137961 to MOF).
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