Quantum-Mechanical Analysis
of the Energetic Contributions
to π Stacking in Nucleic Acids versus Rise, Twist, and Slide
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Abstract
Symmetry-adapted perturbation theory (SAPT) is applied
to pairs
of hydrogen-bonded nucleobases to obtain the energetic components
of base stacking (electrostatic, exchange-repulsion, induction/polarization,
and London dispersion interactions) and how they vary as a function
of the helical parameters Rise, Twist, and Slide. Computed average
values of Rise and Twist agree well with experimental data for B-form
DNA from the Nucleic Acids Database, even though the model computations
omitted the backbone atoms (suggesting that the backbone in B-form
DNA is compatible with having the bases adopt their ideal stacking
geometries). London dispersion forces are the most important attractive
component in base stacking, followed by electrostatic interactions.
At values of Rise typical of those in DNA (3.36 Å), the electrostatic
contribution is nearly always attractive, providing further evidence
for the importance of charge-penetration effects in π–π
interactions (a term neglected in classical force fields). Comparison
of the computed stacking energies with those from model complexes
made of the “parent” nucleobases purine and 2-pyrimidone
indicates that chemical substituents in DNA and RNA account for 20–40%
of the base-stacking energy. A lack of correspondence between the
SAPT results and experiment for Slide in RNA base-pair steps suggests
that the backbone plays a larger role in determining stacking geometries
in RNA than in B-form DNA. In comparisons of base-pair steps with
thymine versus uracil, the thymine methyl group tends to enhance the
strength of the stacking interaction through a combination of dispersion
and electrosatic interactions