title: Accurate ab initio prediction of NMR chemical shifts of nucleic acids and nucleic acids/protein complexes.
abstract: 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 (r(2)) 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.
authors.affiliation: Department of Chemistry and Zukunftskolleg, Universität Konstanz, 78457 Konstanz, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Victora
authors.affiliation: Institute of Chemistry, University of Potsdam, Karl-Liebknecht-Strasse 24-25, 14476 Potsdam OT Golm, Germany.
authors.forename: Heiko M
authors.initials: HM
authors.lastname: Möller
authors.affiliation: Department of Chemistry and Zukunftskolleg, Universität Konstanz, 78457 Konstanz, Germany Institute of Pharmacy, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany Thomas.Exner@uni-tuebingen.de.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Exner
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D054856:G-Quadruplexes; D056968:Lac Repressors / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D009875:Operator Regions, Genetic; D063065:Organophosphonates / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011522:Protons
chemical_list: D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D056968:Lac Repressors; D063065:Organophosphonates; D011522:Protons; D003596:Cytosine; D004247:DNA; D000077404:Cidofovir