Rotational diffusion tensor of nucleic acids from 13C NMR relaxation

Rotational diffusion properties have been derived for the DNA dodecamer d(CGCGAATTCGCG)₂ from ¹³C R₁ and R₁ measurements on the C₁, C₃, and C₄ carbons in samples uniformly enriched in ¹³C. The narrow range of C-H bond vector orientations relative to the DNA axis make the analysis particularly sensitive to small structural deviations. As a result, the R₁/R₁ ratios are found to fit poorly to the crystal structures of this dodecamer, but well to a recent solution NMR structure, determined in liquid crystalline media, even though globally the structures are quite similar. A fit of the R₁/R₁ ratios to the solution structure is optimal for an axially symmetric rotational diffusion model, with a diffusion anisotropy, D_||/D, of 2.1±0.4, and an overall rotational correlation time, (2D_||+4D)^–1, of 3.35 ns at 35 °C in D₂O, in excellent agreement with values obtained from hydrodynamic modeling.     

Overall structure and sugar dynamics of a DNA dodecamer from homo- and heteronuclear dipolar couplings and 31P chemical shift anisotropy

The solution structure of d(CGCGAATTCGCG)₂ has been determined on the basis of an exceptionally large set of residual dipolar couplings. In addition to the heteronuclear ¹³C-¹H and ¹⁵N-¹H and qualitative homonuclear ¹H-¹H dipolar couplings, previously measured in bicelle medium, more than 300 quantitative ¹H-¹H and 22 ³¹P-¹H dipolar restraints were obtained in liquid crystalline Pf1 medium, and 22 ³¹P chemical shift anisotropy restraints. High quality DNA structures can be obtained solely on the basis of these new restraints, and these structures are in close agreement with those calculated previously on the basis of ¹³C-¹H and ¹⁵N-¹H dipolar couplings. In the newly calculated structures, ³¹P-¹H dipolar and ³Jsub H3 P sub couplings and ³¹P CSA data restrain the phosphodiester backbone torsion angles. The final structure represents a quite regular B-form helix with a modest bending of 10°, which is essentially independent of whether or not electrostatic terms are used in the calculation. Combined, the number of homo- and heteronuclear dipolar couplings significantly exceeds the number of degrees of freedom in the system. Results indicate that the dipolar coupling data cannot be fit by a single structure, but are compatible with the presence of rapid equilibria between C2-endo and C3-endo deoxyribose puckers (sugar switching). The C2-H2/H2 dipolar couplings in B-form DNA are particularly sensitive to sugar pucker and yield the largest discrepancies when fit to a single structure. To resolve these discrepancies, we suggest a simplified dipolar coupling analysis that yields N/S equilibria for the ribose sugar puckers, which are in good agreement with previous analyses of NMR J_HH couplings, with a population of the minor C3-endo form higher for pyrimidines than for purines.     

H···N hydrogen bond lengths in double stranded DNA from internucleotide dipolar couplings

The ratio of the internucleotide dipolar coupling and the corresponding one-bond imino ¹⁵N-¹H dipolar coupling provides a measure for the N···H/H-N distance ratio. Measurements were carried out for a dodecamer, d(CGCGAATTCGCG)₂, in which a C-G and an A-T basepair were uniformly enriched in ¹⁵N. When assuming H-bonds to be perfectly linear, dipolar data indicate time-averaged hydrogen bond lengths of 1.80±0.03 Å for A-T and 1.86±0.02 Å for C-G. When using H-bond orientations from high resolution X-ray data, H-bond lengths are about 0.1 Å shorter.     

Measurement of 1H3′-31P dipolar couplings in a DNA oligonucleotide by constant-time NOESY difference spectroscopy

The ratios of cross peak intensities in a selective constant-time NOESY experiment, recorded with and without ³¹P decoupling, yield values for the sum of the H3-P scalar and dipolar couplings. The selective refocusing of H3 resonances in this experiment results in excellent resolution and sensitivity, even in the liquid crystalline phase where the ¹H spectrum is broadened by unresolved homonuclear dipolar couplings. The vicinal H3-P scalar and dipolar couplings in the DNA oligomer d(CGCGAATTCGCG)₂ were measured in both isotropic solution, and in a liquid crystalline phase. Isotropic values are in good agreement with values reported previously. Dipolar couplings are in excellent agreement with the NMR structure for this dodecamer, and to a somewhat lesser extent with the X-ray structures.     

Molecular dynamic simulation and DFT study on the Drug-DNA interaction; Crocetin as an anti-cancer and DNA nanostructure model

In this research, the interaction of Crocetin as an anti-cancer drug and a Dickerson DNA has been investigated. 25 ns molecular dynamic simulations of Crocetin and DNA composed of 12 base pairs and a sequence of d(CGCGAATTCGCG)₂ were done in water. Three definite parts of the B-DNA were considered in analyzing the best interactive site from the thermodynamic point of view. Binding energy analysis showed that van der Waals interaction is the most important part related to the reciprocal O and H atoms of the Crocetin and DNA. Stabilizing interactions, obtained by ΔG calculations, showed that maximum and minimum interactions are related to the S1 and S3 regions, respectively. This means that the most probable van der Waals interaction site of the Dickerson B-DNA and Crocetin is located in the minor groove of DNA. Two sharp peaks at 2.55 and 1.75 Å in radial distribution functions of the PO?HO and NH?OC parts are related to new hydrogen bonds between the Crocetin and DNA in the complex which can be considered as the driving force of the anti-cancer mechanism of the Crocetin. Average values of 0.3 au and zero for the electron densities of the H?O bonds for DNA and complex, obtained by Quantum theory of atoms in molecules (QTAIM), means that the origin of DNA instability after complexation may be related to the H-bond denaturation by Crocetin. Finally, the evaluation of the dispersion interactions using the dispersion functional, -148.76 kcal.mol^?1, confirmed the importance of the dispersion interaction in drug-DNA complex.