Hydrogen Bonding and Stacking of DNA Bases: A Review of Quantum-chemicalab initioStudies

Abstract

Ab initio quantum-chemical calulations with inclusion of electron correlation made since 1994 (such reliable calculations were not feasible before) significantly modified our view on interactions of nucleic acid bases. These calculations allowed to perform the first reliable comparison of the strength of stacked and hydrogen bonded pairs of nucleic acid bases, and to characterize the nature of the base-base interactions. Although hydrogen-bonded complexes of nucleobases are primarily stabilized by the electrostatic interaction, the dispersion attraction is also important. The stacked pairs are stabilized by dispersion attraction, however, the mutual orientation of stacked bases is determined rather by the electrostatic energy. Some popular theories of stacking were ruled out: The theory based on attractive interactions of polar exocyclic groups of bases with delocalized electrons of the aromatic rings (Bugg et al., Biopolymers 10, 175 (1971), and the pi-pi interactions model (C.A. Hunter, J. Mol. Biol. 230, 1025 (1993)). The calculations demonstrated that amino groups of nucleobases are very flexible and intrinsically nonplanar, allowing hydrogen-bond-like interactions which are oriented out of the plane of the nucleobase. Many H-bonded DNA base pairs are intrinsically nonplanar. Higher-level ab initio calculations provide a unique set of reliable and consistent data for parametrization and verification of empirical potentials. In this article, we present a short survey of the recent calculations, and discuss their significance and limitations. This summary is written for readers which are not experts in computational quantum chemistry.

Density functional study of guanine and uracil quartets and of guanine quartet/metal ion complexes

“…We discuss first the calculated quartet properties obtained with the B3LYP method and Pople-type basis sets, because the 6-31G(d,p) basis has been used frequently for base pairs. 1,11,14,15,51 In a subsequent section we compare the results obtained with B3LYP and different basis sets, and then we discuss the data obtained with the different DFT methods and a common basis set.…”

“…For quantum chemical studies of base pairs Hartree-Fock (HF) theory and Møller-Plesset perturbation theory of second order (MP2) have been used frequently, whereas for individual bases higher theoretical levels have been adopted. 1 As the computational demand increases rapidly with the number of bases, density functional theory (DFT) appears to be an attractive alternative for nucleic acid model systems. The application of DFT methods has provided promising results for individual fragments of organic and biomolecular structures.…”

Collision-induced dissociation of 16-mer DNA duplexes with various sequences: evidence for conservation of the double helix conformation in the gas phase

“…Finally, adjacent bases are also interacting with each other electrostatically (dipole-dipole, short range interactions) and these interactions are favored in the double helix for conformational reasons. This kind of interaction is called "base stacking" (22) and is sequence-dependent. Here we present a more extensive MS/MS study of complexes of various sequences that strongly indicates that base stacking shortrange interactions are conserved in the gas-phase duplexes.…”

Effects of structural variations on the hydrogen bond pairing between adenine derivatives and thymine

“…Hydrogen bonding [1][2][3][4] plays a key role in various biological processes, including pairing of nucleobases [4,6], protein folding [7,8], enzyme catalysis [9,10], and other interactions in biosystems. Hydrogen bonding influences the solubility of biologically active ligands and the way they bind to bioreceptors [11].…”