Calculating the Response of NMR Shielding Tensor σ(31P) and 2J(31P,13C) Coupling Constants in Nucleic Acid Phosphate to Coordination of the Mg2+ Cation

Dependence of NMR P-31 shielding tensor and (2)J(P,C) coupling constants on solvation of nucleic acid phosphate by Mg2+ and water was studied using methods of bioinformatic structural analyses of crystallographic data and DFT B3LYP calculations of NMR parameters. The effect of solvent dynamics on NMR parameters was calculated using molecular dynamic. The NMR calculations for representative solvation patterns determined in crystals of B-DNA and A-RNA molecules pointed out the crucial importance of local Mg2+ coordination geometry, including hydration by explicit water molecules and necessity of dynamical averaging over the solvent reorientation. The dynamically averaged P-31 chemical shift decreased by 2-9.5 ppm upon Mg2+ coordination, the chemical shielding anisotropy increased by 0-20 ppm, and the (2)J(P,C5') coupling magnitude decreased by 0.2-1.8 Hz upon Mg2+ coordination. The calculated decrease of the P-31 chemical shift is in excellent agreement with the 1.5-10 ppm decrease of the phosphorothioate P-31 chemical shift upon Cd2+ coordination probed experimentally in hammerhead ribozyme (Suzumura; et al. J. Am. Chem. Soc. 2002, 124, 8230-8236; Osborne; et al., Biochemistry 2009, 48, 10654-10664). None of the dynamically averaged NMR parameters unequivocally distinguishes the site-specific Mg2+ coordination to one of the two nonesterified phosphate oxygen atoms of the phosphate determined by bioinformatic analyses. By comparing the limit cases of static and dynamically averaged solvation, we propose that mobility of the solvent has a dramatic impact on NMR parameters of nucleic acid phosphate and must be taken into account for their accurate modeling.