Gas-phase conformations of deprotonated and protonated mononucleotides determined by ion mobility and theoretical modeling

Collision cross-sections of protonated and deprotonated 2'-deoxy-5'-mononucleotide ions were measured in helium using ion mobility based methods. Various computational methods were then used to generate candidate structures of the ions and calculate their collision cross-sections for comparison to experiment. For the deprotonated systems, the ion mobility data indicate that only one family of conformers is present. Molecular mechanics calculations (AMBER) predict that the sugar is twisted into a C-3'-endo conformation with the phosphate and base above the plane of the sugar. For dAMP, dCMP, and dTMP, the base is in an "anti" conformation about the glycosidic bond but in dGMP, the guanine base is in a "syn" position with the amino group hydrogen-bonded to the deprotonated phosphate. DFT calculations yield similar low-energy structures as those predicted by AMBER. The calculated cross-sections of the C-3'-endo conformers agree very well with experimental values (1-2% difference). For the protonated mononucleotides, the ion mobility results also indicate that only one family of conformers is present. However, unlike the deprotonated systems, theory predicts that the sugars and the bases are in an opposite orientation (C-2'-endo VS C-3'-endo and syn vs anti) with respect to how they are positioned in the deprotonated series. DFT calculations predict that the lowest energy structures are protonated at N3 in dAMP, N7 in dGMP, N3 in dCMP, and the phosphate group in dTMP. AMBER calculations, with the bases protonated at the DFT predicted sites, yield structures that agree very well with experiment (1-2% difference).