Characterization of the base stacking interactions in DNA by means of Lennard-Jones empirical potentials

Three empirical potentials of the Lennard-Jones type taken from literature were used to calculate van der Waals contributions to the base-pair couples stacking energies in B-DNA and A-DNA type double helical conformations. The information obtained can be summarized as follows: (1) Purine-pyrimidine and purine-purine (pyrimidine-pyrimidine in the complementary strand) sequences preferred right-handed helical arrangement, whereas pyrimidine-purine sequences favoured left-handed (C-G) or unwound (T-A) stacking geometry; in the latter case this only held for B- but not A-DNA (the C-G sequence was not studied in A-DNA owing to difficulties (see below) with the G amino group in B-DNA); (2) Positive propeller twist of base-pairs was stable in both B- and A-DNA; the thymine methyl group promoted the propeller and this effect was strongest in the A-T step; (3) Tilt of base pairs occurred around zero in B-DNA and between 15-20 degrees C in A-DNA, in agreement with the experimental observations; (4) Vertical separation of base pairs was optimal within 0.33-0.34 nm for B-DNA and around 0.29 nm for A-DNA using the 9-6 potential. The 12-6 potential gave similar results with B-DNA as the 9-6 potential if, however, base pairs were separated by 0.35-0.36 nm; (5) The calculated effect of the guanine amino group was substantially stronger than expected on the basis of data derived from X-ray diffraction studies of oligonucleotide single crystals; (6) In comparison with the 9-6 potential, the 12-6 potential provided more strict energy minima. In summary, the empirical potentials reproduce, at least semiquantitatively, many but not all DNA properties; this should be taken into account whenever the potentials are used for prediction purposes.