Prediction of (19)F NMR Chemical Shifts in Labeled Proteins: Computational Protocol and Case Study.
Related Articles Prediction of (19)F NMR Chemical Shifts in Labeled Proteins: Computational Protocol and Case Study.
Mol Pharm. 2016 May 24;
Authors: Isley Iii WC, Urick AK, Pomerantz WC, Cramer CJ
Abstract
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 (19)F NMR for screening low molecular weight molecules (i.e., fragments) can be an especially powerful tool to aid in drug design. NMR resonance assignment of the protein's (19)F 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 (19)F 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.
PMID: 27218275 [PubMed - as supplied by publisher]
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