Density functional study of guanine quartet structures

Michael Meyer¹, Thomas Steinke¹,Jürgen Sühnel² and Maria Brandl²

Quantum chemical studies of base pairs provide an accurate description of Watson-Crick and non-standard base pairs at Hartree-Fock and MP2 level [Sponer et al., 1996; Meyer et al., 1997; Brandl et al., 1996]. Density functional calculations are an efficient alternative to these classical methods for the investigation of hydrogen bonded bases. We have used the B3LYP hybrid density functional method [Becke, 1993; Lee et al., 1998] to analyse guanine quartet structures. Guanine forms quartet structures in the unusually stable RNA tetraplex r(UGGGGU) ₄ [Cheong et al., 1992], which has a 4-fold symmetry axis, and in guanine rich telomeric DNA. The center of these quartets has a pocket believed to be the site of interaction with monovalent cations [Williamson, 1994].

We have optimized the guanine quartet structures at B3LYP/6-31G(d,p) and B3LYP/6-311G(d,p) level assuming a C _4h - and S ₄ -symmetry. For the alkali and earth alkali ions the 6-31G(d,p) basis set and effective core potentials have been used [Pacios et al.,1985; Hurley et al., 1986]. Interaction energies have been determined using the coun- terpoise method to correct the basis set superposition error.

Two classical hydrogen bonds, N-H...N7 (1.971 Å) and N1-H...O6 (1.782 Å), exist between each base pair with a Hoogsteen geometry. The non-planar structure with S 4 -symmetry and the planar structure with C _4h -symmetry have approximately the same energy. All complexes of the guanine quartet and cations show a substantial charge transfer between the bases and the ion. In contrast to other alkali and alkaline-earth ions, sodium ions stabilize the planar guanine quartet conformation observed in biopolymers.

The interaction energy within the G-quartet is -75.6 kcal/mol and the pairwise interaction energy between hydrogen bonded neighbour bases amounts to -13.7 kcal/mol. The interaction energy between the non-hydrogen bonded pairs is an order of magnitude smaller than the one of the hydrogen bonded pairs. Furthermore, the cooperative part of the interaction energy contibutes about 20% of the total interaction energy. The structures and energies derived from effective core potentials are in good agreement with the results obtained with standard basis sets and therefore effective core potentials are promising for quantum chemical studies of bioinorganic compounds.

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