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

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• 作者：Alexander Grishaev ; Jinfa Ying ; Ad Bax
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：April 25, 2012
• 年：2012
• 卷：134
• 期：16
• 页码：6956-6959
• 全文大小：235K
• 年卷期：v.134,no.16(April 25, 2012)
• ISSN：1520-5126

文摘

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鈥揌1 vectors in G and N3鈥揌3 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鈥揌 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鈥揌 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.