Anisotropic flexibility of DNA depends on the base sequence. Conformation calculations of double-stranded tetranucleotides AAAA:TTTT, (AATT)2, (TTAA)2, GGGG:CCCC, (GGCC)2, (CCGG)2

The bending flexibility of six tetramers was studied in an assumption that they were extended in the both directions by regular double helices. The bends of B-DNA in different directions were considered. The stiffness of the B-DNA double helix when bent into the both grooves proved to be less pronounced than in the perpendicular direction by the order of magnitude. Such an anisotropy is a feature of the sugar-phosphate backbone structure. The calculated fluctuations of the DNA bending along the dyad axis, 5-7 degrees, are in agreement with the experimental value of DNA persistence length. Anisotropy of the double helix is sequence-dependent: most easily bent into the minor groove are the tetramers with purine-pyrimidine dimer (RY) in the middle. In contrast, YR dinucleotides prefer bending into the major groove, moreover, they have an equilibrium bend of 6-12 degrees into this groove. The above inequality is caused by the stacking interaction of the bases. The bend in the central dimers is distributed to some extent between the adjacent links, though the main fraction of the bend remains within the central link. Variation of the sugar-phosphate geometry in the bent helix is unessential, so that DNA remains within the limits of the B-family of forms: namely, when the helical axis is bent by 20 degrees the backbone dihedral angles vary by no more than 15 degrees. The obtained results are in accord with the X-ray structure of B-DNA dodecamer; they further substantiate our earlier model of DNA wrapping in the nucleosome by means of "mini-kinks" separated by a half-pitch of the double helix, i.e. by 5-6 b. p. Sequence-dependent anisotropy of DNA presumably dictates the three-dimensional structure of DNA in solution as well. We have found that nonrandom allocation of YR dimers leads to the systematic bends in the equilibrium structure of certain DNA fragments. To the four "Calladine rules" two more can be added: the minor-groove steric clash of purines in the YR sequences are avoided by: (1) bending of the helix into the major groove; (2) increasing the distance between the base pairs (stretching the double helix).