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Predicting \(^{19}\)F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-214879
- The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable \(^{19}\)F chemical‐shift predictions to deduce ligand‐binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the \(^{19}\)F NMR chemical shifts of aThe absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable \(^{19}\)F chemical‐shift predictions to deduce ligand‐binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the \(^{19}\)F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleeping sickness. We include many protein–inhibitor conformations as well as monomeric and dimeric inhibitor–protein complexes, thus rendering it the largest computational study on chemical shifts of \(^{19}\)F nuclei in a biological context to date. Our predicted shifts agree well with those obtained experimentally and pave the way for future work in this area.…
Autor(en): | Johannes C. B. Dietschreit, Annika Wagner, T. Anh Le, Philipp Klein, Hermann Schindelin, Till Opatz, Bernd Engels, Ute A. Hellmich, Christian Ochsenfeld |
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URN: | urn:nbn:de:bvb:20-opus-214879 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Chemie und Pharmazie / Institut für Physikalische und Theoretische Chemie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Angewandte Chemie International Edition |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 59 |
Heft / Ausgabe: | 31 |
Erste Seite: | 12669 |
Letzte Seite: | 12673 |
Originalveröffentlichung / Quelle: | Angewandte Chemie International Edition 2020, 59(31):12669-12673. DOI: 10.1002/anie.202000539 |
DOI: | https://doi.org/10.1002/anie.202000539 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Freie Schlagwort(e): | African sleeping sickness; NMR spectroscopy; covalent inhibitors; quantum chemistry; structural biology |
Datum der Freischaltung: | 19.04.2021 |
Lizenz (Deutsch): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |