Phosphorus Chemical Shifts in a Nucleic Acid Backbone from Combined Molecular Dynamics and Density Functional Calculations

A comprehensive quantum chemical analysis of the influence of backbone torsion angles on P-31 chemical shifts in DNAs has been carried out. An extensive DFT study employed snapshots obtained from the molecular dynamics simulation of [d(CGCGAATTCGCG)](2) to construct geometries of a hydrated dimethyl phosphate, which was used as a model for the phosphodiester linkage. Our calculations provided differences of 2.1 +/- 0.3 and 1.6 +/- 0.3 ppm between the B-I and B-II chemical shifts in two B-DNA residues of interest, which is in a very good agreement with the difference of 1.6 ppm inferred from experimental data. A more negative P-31 chemical shift for a residue in pure B-I conformation compared to residues in mixed B-I/B-II conformation states is provided by DFT, in agreement with the NMR experiment. Statistical analysis of the MD/DFT data revealed a large dispersion of chemical shifts in both B-I and B-II regions of DNA structures. delta P ranges within 3.5 +/- 0.8 ppm in the B-I region and within 4.5 +/- 1.5 ppm in the B-II region. While the P-31 chemical shift becomes more negative with increasing a in B-I-DNA, it has the opposite trend in B-II-DNA when both a and zeta increase simultaneously. The P-31 chemical shift is dominated by the torsion angles a and while an implicit treatment of beta and epsilon is sufficient. The presence of an explicit solvent leads to a damping and a 2-3 ppm upfield shift of the torsion angle dependences.