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

• Published in: Journal of the American Chemical Society 2010-12, Vol.132 (48), p.17139-17148
• Main Authors: Přecechtělová, Jana, Novák, Petr, Munzarová, Markéta L, Kaupp, Martin, Sklenář, Vladimír
• Format: Article
• Language: English
• Subjects: Base Sequence; DNA, B-Form - chemistry; DNA, B-Form - genetics; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Dynamics Simulation; Phosphorus - chemistry; Quantum Theory; Rotation
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja104564g

A comprehensive quantum chemical analysis of the influence of backbone torsion angles on 31P 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 BI and BII 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 31P chemical shift for a residue in pure BI conformation compared to residues in mixed BI/BII 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 BI and BII regions of DNA structures. δP ranges within 3.5 ± 0.8 ppm in the BI region and within 4.5 ± 1.5 ppm in the BII region. While the 31P chemical shift becomes more negative with increasing α in BI-DNA, it has the opposite trend in BII-DNA when both α and ζ increase simultaneously. The 31P chemical shift is dominated by the torsion angles α and ζ, while an implicit treatment of β and ε is sufficient. The presence of an explicit solvent leads to a damping and a 2−3 ppm upfield shift of the torsion angle dependences.