Imino hydrogen positions in nucleic acids from density functional theory validated by NMR residual dipolar couplings.

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleImino hydrogen positions in nucleic acids from density functional theory validated by NMR residual dipolar couplings.
Publication TypeJournal Article
Year of Publication2012
AuthorsGrishaev, A, Ying, J, Bax, A
JournalJ Am Chem Soc
Volume134
Issue16
Pagination6956-9
Date Published2012 Apr 25
ISSN1520-5126
KeywordsCrystallography, X-Ray, Hydrogen, Hydrogen Bonding, Imines, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Nucleic Acids, Quantum Theory
Abstract

Hydrogen 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.

DOI10.1021/ja301775j
Alternate JournalJ. Am. Chem. Soc.
PubMed ID22489834
PubMed Central IDPMC3337690
Grant List / / Intramural NIH HHS / United States