Journal Article

Accurate <i>ab initio</i> prediction of NMR chemical shifts of nucleic acids and nucleic acids/protein complexes

Andrea Victora, Heiko M. Möller and Thomas E. Exner

in Nucleic Acids Research

Volume 42, issue 22, pages e173-e173
Published in print December 2014 | ISSN: 0305-1048
Published online November 2014 | e-ISSN: 1362-4962 | DOI: http://dx.doi.org/10.1093/nar/gku1006

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NMR chemical shift predictions based on empirical methods are nowadays indispensable tools during resonance assignment and 3D structure calculation of proteins. However, owing to the very limited statistical data basis, such methods are still in their infancy in the field of nucleic acids, especially when non-canonical structures and nucleic acid complexes are considered. Here, we present an ab initio approach for predicting proton chemical shifts of arbitrary nucleic acid structures based on state-of-the-art fragment-based quantum chemical calculations. We tested our prediction method on a diverse set of nucleic acid structures including double-stranded DNA, hairpins, DNA/protein complexes and chemically-modified DNA. Overall, our quantum chemical calculations yield highly/very accurate predictions with mean absolute deviations of 0.3–0.6 ppm and correlation coefficients (r2) usually above 0.9. This will allow for identifying misassignments and validating 3D structures. Furthermore, our calculations reveal that chemical shifts of protons involved in hydrogen bonding are predicted significantly less accurately. This is in part caused by insufficient inclusion of solvation effects. However, it also points toward shortcomings of current force fields used for structure determination of nucleic acids. Our quantum chemical calculations could therefore provide input for force field optimization.

Journal Article.  7813 words.  Illustrated.

Subjects: Molecular and Cell Biology ; Proteins ; Molecular Biology and Genetics

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