Sugar phosphate backbone conformations are a structural element inextricably involved in a complete understanding of specific recognition nucleic acid ligand interactions, from early stage discrimination of the correct target to complexation per se, including any structural adaptation on binding. The collective results of high resolution DNA, RNA and protein/DNA crystal structures provide an opportunity for an improved and enhanced statistical analysis of standard and unusual sugar-phosphate backbone conformations together with corresponding dinucleotide sequence effects as a basis for further exploration of conformational effects on binding. In this study, we have analyzed the conformations of all relevant crystal structures in the nucleic acids data base, determined the frequency distribution of all possible epsilon, zeta, alpha, beta and gamma backbone angle arrangements within four nucleic acid categories (A-RNA and A-DNA, free and bound B-DNA) and explored the relationships between backbone angles, sugar puckers and selected helical parameters. The trends in the correlations are found to be similar regardless of the nucleic acid category. It is interesting that specific structural effects exhibited by the different unusual backbone sub-states are in some cases contravariant. Certain alpha/gamma changes are accompanied by C3' endo (north) sugars, small twist angles and positive values of base pair roll, and favor a displacement of nucleotide bases towards the minor groove compared to that of canonical B form structures. Unusual epsilon/zeta combinations occur with C2' (south) sugars, high twist angles, negative values of base pair roll, and base displacements towards the major groove. Furthermore, any unusual backbone correlates with a reduced dispersion of equilibrium structural parameters of the whole double helix, as evidenced by the reduced standard deviations of almost all conformational parameters. Finally, a strong sequence effect is displayed in the free oligomers, but reduced somewhat in the ligand bound forms. The most variable steps are GpA and CpA, and, to a lesser extent, their partners TpC and TpG. The results provide a basis for considering if the variable and non-variable steps within a biological active sequence precisely determine morphological structural features as the curvature direction, the groove depth, and the accessibility of base pair for non covalent associations.

In the crystal structures of protein complexes with B-DNA, alpha and gamma DNA backbone torsion angles often exhibit non-canonical values. It is not known if these alternative backbone conformations are easily accessible in solution and can contribute to the specific recognition of DNA by proteins. We have analysed the coupled transition of the alpha and gamma torsion angles within the central GpC step of a B-DNA dodecamer by computer simulations. Five stable or metastable non-canonical alpha/gamma sub-states are found. The most favourable pathway from the canonical alpha/gamma structure to any unusual form involves a counter-rotation of alpha and gamma, via the trans conformation. However, the corresponding free energy indicates that spontaneous flipping of the torsions is improbable in free B-DNA. This is supported by an analysis of the available high resolution crystallographic structures showing that unusual alpha/gamma states are only encountered in B-DNA complexed to proteins. An analysis of the structural consequences of alpha/gamma transitions shows that the non-canonical backbone geometry influences essentially the roll and twist values and reduces the equilibrium dispersion of structural parameters. Our results support the hypothesis that unusual alpha/gamma backbones arise during protein-DNA complexation, assisting the fine structural adjustments between the two partners and playing a role in the overall complexation free energy.