Time evolution of NMR proton chemical shifts of an RNA hairpin during a molecular dynamics simulation

We have calculated the time evolution of three nonlocal contributions to the proton chemical shifts of a ribonucleic acid: ring current effects, intramolecular electrostatic shifts, and electrostatic shifts due to solvent. The computation was done on a 1.075 ns molecular dynamics trajectory of a fully solvated RNA hairpin with sodium counterions. The calculated shift components exhibit rapid fluctuations on a subpicosecond time scale. The magnitudes of fluctuations are dependent on two factors: the proximity of a shift source and the dynamics of the local RNA structure. The largest fluctuations were found for the shifts of exchangeable protons due to the electrostatic effects of hydrogen bond accepters. The magnitudes of the time-averaged shifts differ significantly for the ring current and intramolecular electrostatic contributions in a structure-dependent manner. For the ribose and exchangeable aromatic protons, the major contributor to the total chemical shift is the intramolecular electrostatic effect, whereas nonexchangeable aromatic proton shifts are equally affected by ring current effects and intramolecular electrostatic shifts. Changes in the ribose sugar pucker cause large changes in the nonlocal contributions to the chemical shifts of the H2', H3', and H4' protons. Empirical values of local chemical shifts provided good agreement between calculated and measured shifts for the nonexchangeable aromatic protons when the solvent contributions were excluded from the calculation.