DNA base-stacking interactions: a comparison of theoretical calculations with oligonucleotide X-ray crystal...

Experimental data on the conformational properties of dinucleotides taken from high-resolution X-ray crystal structures of oligonucleotides have been compared with theoretical energy calculations on the base-stacking interactions. The conformational properties of the dinucleotides determined by calculation agree well with the experimental data, which shows that the method used for computing the stacking interactions is reliable. In addition, the calculations provide insight into the origins of the major trends that are observed in the experimental data. The values of the step parameters roll, tilt and rise, are determined entirely by the van der Waals interactions, and this reflects the strong requirement that the bases remain stacked in close contact. Slide, shift and twist do not affect the vertical separation of the bases and are therefore less tightly constrained. Electrostatic interactions play an important role in determining the values of shift and slide, but the base-stacking interaction energy is essentially independent of the value of twist. Thus the experimental value of twist is most likely fixed by the constraints of the backbone, which are missing in these calculations.