Prediction of 19F NMR chemical shifts in labeled proteins: Computational protocol and case study

William C. Isley, Andrew K. Urick, William C Pomerantz, Chris Cramer

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


The structural analysis of ligand complexation in biomolecular systems is important in the design of new medicinal therapeutic agents; however, monitoring subtle structural changes in a protein's microenvironment is a challenging and complex problem. In this regard, the use of protein-based 19F NMR for screening low-molecular-weight molecules (i.e., fragments) can be an especially powerful tool to aid in drug design. Resonance assignment of the protein's 19F NMR spectrum is necessary for structural analysis. Here, a quantum chemical method has been developed as an initial approach to facilitate the assignment of a fluorinated protein's 19F NMR spectrum. The epigenetic "reader" domain of protein Brd4 was taken as a case study to assess the strengths and limitations of the method. The overall modeling protocol predicts chemical shifts for residues in rigid proteins with good accuracy; proper accounting for explicit solvation of fluorinated residues by water is critical.

Original languageEnglish (US)
Pages (from-to)2376-2386
Number of pages11
JournalMolecular Pharmaceutics
Issue number7
StatePublished - Jul 5 2016

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.


  • DFT
  • F NMR
  • NMR
  • bromodomain
  • fluorine
  • screening


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