## Imino Hydrogen Positions in Nucleic Acids from Density Functional Theory Validated by NMR Residual Dipolar Couplings

journal contribution

posted on 16.12.2015, 21:17 by Alexander Grishaev, Jinfa Ying, Ad BaxHydrogen atom positions of nucleotide bases in RNA structures
solved
by X-ray crystallography are commonly derived from heavy-atom coordinates
by assuming idealized geometries. In particular, N1–H1 vectors
in G and N3–H3 vectors in U are commonly positioned to coincide
with the bisectors of their respective heavy-atom angles. We demonstrate
that quantum-mechanical optimization of the hydrogen positions relative
to their heavy-atom frames considerably improves the fit of experimental
residual dipolar couplings to structural coordinates. The calculations
indicate that deviations of the imino N–H vectors in RNA U
and G bases result from H-bonding within the base pair and are dominated
by the attractive interaction between the H atom and the electron
density surrounding the H-bond-acceptor atom. DFT optimization of
H atom positions is impractical in structural biology studies. We
therefore have developed an empirical relation that predicts imino
N–H vector orientations from the heavy-atom coordinates of
the base pair. This relation agrees very closely with the DFT results,
permitting its routine application in structural studies.