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

摘要

A comprehensive quantum chemical analysis of the influence of backbone torsion angles on ~(31)P 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 ~(31)P chemical shift for a residue in pure B, conformation compared to residues in mixed B|/Bu 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. δP 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 ~(31)P chemical shift becomes more negative with increasing a in B_Ⅰ-DNA, it has the opposite trend in Bh-DNA when both a and ξ increase simultaneously. The ~(31)P chemical shift is dominated by the torsion angles a and ξ, while an implicit treatment of ji and e is sufficient. The presence of an explicit solvent leads to a damping and a 2-3 ppm upfield shift of the torsion angle dependences.