Nucleic acid base stacking

J. Sponer, J. Leszczynski, P. Hobza, Nature of nucleic acid-base stacking Nonempirical ab initio and empirical potential characterization of 10 stacked base dimers. Comparison of stacked and H-bonded base pairs. J. Phys. Chem. 100, 5590-5596 (1996)... 

Morgado, C. A. Jurecka, R Svozil, D. Hobza, R Sponer, J. 1. Balance of attraction and repulsion in nucleic-acid base stacking CCSD(T)/complete-basis-set-limit calculations on uracil dimer and a comparison with the force-field description, J. Chem. Theor. Comput. 2009, 5, 1524-1544. 

Friedman RA, Honig B. A free energy analysis of nucleic acid base stacking in aqueous solution. Biophys. J. 1995 69 1528-1535. 

To estimate the concentration of an oligonucleotide solution, the absorption is measured at 260 nm. Correct weights of solid oligonucleotides are difficult to obtain due to non-stoichio-metric inclusion of water molecules into the solid. UV spectra of nucleic acids exhibit a pronounced hypochromicity. In double-stranded nucleic acids, base stacking with a distance of about 3.5 A lowers UV-absorption by up to 20% due ii-systems interaction when compared with single-stranded oligomers (Fig. 25). 

This resonance interaction requires that the N atom of aromatic amines be sp hybridized and therefore planar, a situation that is critical to nucleic acid base stacking and hydrogen bonding. 

Dill KA (1997) Additivity principles in biochemistry. J Biol Chem 272(2) 701-704 McKay SL, Haptonstall B, Gellman SH (2001) Beyond the hydrophobic effect attractions involving heteroaromatic rings in aqueous solution. J Am Chem Soc 123(6) 1244-1245 Luo R, Gilson HSR., Potter MJ, Gilson MK (2001) The physical basis of nucleic acid base stacking in water. Biophys J 80(1) 140 148... 

A hypochromicity was observed between THPVP and APVP (or TPVP). Since theophylline is not a nucleic acid base and does not form hydrogen-bonding, these observations indicate that stacking-type hydrophobic forces are important. 

Fig. 10 Charge transport is observed in a variety of nucleic acid assemblies over a wide distance regime (3.4-200 A). Shown are examples of nucleic acid structures through which charge transport has been examined a B-form DNA b DNA-RNA hybrids c cross-over junctions and d nucleosome core particles. In all assemblies, the charge transport chemistry is extremely sensitive to the structure of the -stacked nucleic acid bases...

The fluorescence of 2AP is strongly quenched by nucleic acid bases [17, 18, 24-29]. Time-correlated single-photon counting studies have shown that the interactions of 2AP with different nucleic acid bases significantly decrease the 2AP fluorescence hfetime [17, 24-29]. While the fluorescence lifetime of free 2AP in aqueous solution is about 10 ns, in double-stranded DNA the 2AP hfetimes are reduced to 30-50 ps. This effect has been used extensively to study the dynamics of mismatched base pairs [19, 21, 25, 30], local changes in dynamics of DNA molecules produced by their binding to the active sites of polymerases [26, 31-33], stacking interactions at abasic... 

The purine and pyrimidine bases are hydrophobic and relatively insoluble in water at the near-neutral pH of the cell. At acidic or alkaline pH the bases become charged and their solubility in water increases. Hydrophobic stacking interactions in which two or more bases are positioned with the planes of their rings parallel (like a stack of coins) are one of two important modes of interaction between bases in nucleic acids. The stacking also involves a combination of van der Waals and dipole-dipole interactions between the bases. Base stacking helps to minimize contact of the bases with water, and base-stacking interactions are very important in stabilizing the three-dimensional structure of nucleic acids, as described later. 

Heavier metal ions and metal complexes can find sites on nitrogen atoms of the nucleic acid bases. Examples are the platinum complex cisplatin and the DNA-cleaving antibiotic neocarzinostatin (Box 5-B). Can metals interact with the n electrons of stacked DNA bases A surprising result has been reported for intercalating complexes of ruthenium (Ru) and rhodium (Rh). Apparent transfer of electrons between Ru (II) and Rh (III) over distances in excess of 4.0 nm, presumably through the stacked bases, has been observed,181 as has electron transfer from other ions.181a Stacked bases are apparently semiconductors.182... 

Nucleic acids can be visualized on the slab gel after separation by soaking in a solution of ethidium bromide, a dye that displays enhanced fluorescence when intercalated between stacked nucleic acid bases. Ethidium bromide may be added directly to the agarose solution before gel formation. This method allows monitoring of nucleic acids during electrophoresis. Irradiation of ethidium bromide-treated gels by UV light results in orange-red bands where nucleic acids are present. 

Because of the efficiency, the density functional theory also became an object of interest for the purpose of evaluation of intermolecular interaction energies for nucleic acid base complexes. Most standard functionals provide qualitatively a good picture of interactions in H-bonded nucleic acid base pairs. However, they completely fail for stacked complexes. This is due to the inability of current functionals to describe correctly the dispersion energy. Several routes were proposed to alleviate this deficiency with different rates of success [9-12],... 

Contrary to H-bonded nucleic acid base pairs discussed in the previous section, the nature of intermolecular interactions in complexes of stacked bases was analyzed more extensively. The values of minimal, maximal, and average total stabilization energies, corrected for BSSE, for a set comprising over 80 stacked bases, are plotted in Fig. 20.1. In the case of guanine-adenine and adenine-cytosine complexes, the results are presented for two sequence contexts, i.e., A/G-G/A and A/C-C/A. The symbol AA denotes the 2-oxo-adenine - complexes of oxidized bases, and this... 

Fig. 20.1 The average, the maximal and the minimal values of intermolecular interaction energy for stacked nucleic acid base complexes calculated at the MP2/aug-cc-pVDZ level of theory...

In this article, we discussed several rigorous ab initio studies, including our own findings, which had recently put the discussion of the nature of intermolecular interactions in nucleic acid base complexes on quantitative basis. The results of computations summarized herein confirm that H-bonded and stacked base pairs are mainly stabilized by electrostatic/delocalization components and dispersion... 

I. Dqbkowska, H.V. Gonzales, P. Jurecka, P. Hobza, Stabilization energies of the hydrogen-bonded and stacked stmctures of nucleic acid base pairs in the crystal geometries of CG, AT, and AC DNA steps and in the NMR geometry of the 5,-d(GCGAAGC)-3 hairpin Complete basis set calculations at the MP2 and CCSD(T) levels. J. Phys. Chem. A 109, 1131-1136 (2005)... 

M. Elstner, P. Hobza, T. Frauenheim, S. Suhai, E. Kaxiras, Hydrogen bonding and stacking interactions of nucleic acid base pairs A density-functional-theory based treatment. J. Chem. Phys. 114, 5149-5155 (2001)... 

J. Sponer, K.E. Riley, P. Hobza, Nature and magnitude of aromatic stacking of nucleic acid bases. Phys. Chem. Chem. Phys. 10, 2595-2610 (2008)... 

P. Hobza et al., Significant structural deformation of nucleic acid bases in stacked base pairs an ab initio study beyond Hartree-Fock. Chem. Phys. Lett. 288, 7-14 (1998)... 

From a chemical perspective, the double-helix produced by two intertwining strands of oligomeric DNA is a fascinating and unique molecular structure. (See Fig. 1 for a structural model of a 12-base pair duplex of B-form DNA.) In it nucleic acid bases are stacked in pairs one on top of the other with a slight twist reminiscent of a spiral staircase [16]. The unique stacking and overlapping of the n- and Tr-electrons of DNA bases may provide a preferred path for electron transfer. Similarly, the exceptional closeness of the stacked bases may have important consequences for charge motion in DNA duplexes. Additionally, the... 

Figure 1 Molecular model of a 12-base pair duplex of canonical B-form DNA. The two 12-mer strands that intertwine to form the duplex are colored separately (black and gray). Nucleic acid base pairs are stacked perpendicular to the helical axis at 3.4-A intervals (center-to-center distance), and the duplex helix repeats its spiral structure every 10 base pairs. (Figure provided by Dr. Carolyn Kanagy using the Sybyl Version 6.3 molecular modeling program from Tripos, Inc. and standard B-form DNA substructures.)...

---