[NMR paper] Predicting 19 F NMR chemical shifts: A combined computational and experimental study of a trypasonomal oxidoreductase-inhibitor complex.

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Predicting 19 F NMR chemical shifts: A combined computational and experimental study of a trypasonomal oxidoreductase-inhibitor complex.

Related Articles Predicting 19 F NMR chemical shifts: A combined computational and experimental study of a trypasonomal oxidoreductase-inhibitor complex.

Angew Chem Int Ed Engl. 2020 Apr 02;:

Authors: Dietschreit J, Wagner A, Le TA, Klein P, Schindelin H, Opatz T, Engels B, Hellmich U, Ochsenfeld C

Abstract
Fluorine's absence 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 19F chemical shift predictions to deduce ligand binding modes hold great potential for in silico drug design. Here, we present a systematic QM/MM study to predict the 19F 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 19F 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.


PMID: 32239740 [PubMed - as supplied by publisher]



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