DFT study of minimal fragments of nucleic acid single chain for explication of sequence dependence of DNA duplex conformation

DFT studies of desoxydinucleoside monophosphate complexes with Na-ions (dDMPs), using DGAUSS and ADF software reveal that the characteristic B-type conformation of DNA duplexes is initially predisposed in single strand in the form of a local minimum. Such predisposition may be important for biological functioning of DNA by facilitating an addition of new nucleotide in the processes of DNA duplication and restoration of double helix after unwinding. The computational results demonstrate the important contribution of intra-strand interactions to conformational stability and sequence-dependent variability of B-DNA duplexes. The main characteristics of the “canonical” BI conformations, such as the regions of torsion angles of sugar-phosphate backbone, C2′-endo or very close to C2′-endo sugar puckerings, and nearly parallel base-ring arrangements are already present in the single strand and are universal for all 16 dDMPs. The dihedral angle between the bases does not depend on the extent of their overlap, which suggests the major contribution of sugar-phosphate backbone to formation of these minima. The study reveals characteristic sequence dependence of the base arrangements. Namely, an extensive base-ring overlap takes place for all purine-purine and purine-pyrimidine sequences, and negligible ring overlap is observed in all pyrimidine-purine and pyrimidine-pyrimidine sequences. These arrangements closely resemble the geometrical characteristics of BI DNA in duplex crystals. Preliminary results of search for other energy minima related to helical DNA structures revealed the existence of BII-like minima for some dDMPs.