Investigations of Biomolecular Conformation and Dynamics using ¹⁹F NMR

Fluorine NMR is a useful probe of protein structure, conformation and folding in fluorinated proteins, owing to the high sensitivity, large chemical shift of the ¹⁹F nucleus and the lack of high background signal to be suppressed. Protein NMR studies using fluorinated amino acids are a valuable addition to the existing suite of experiments with isotopically enriched nuclei. Recently, there have been several efforts to develop novel methods of biosynthetically tagging proteins to contain ¹⁹F labels using fluorinated amino acids. Each fluorine signal in the resultant protein then becomes a reporter of the protein’s structure and conformational dynamics. ¹⁹F NMR relaxation times (including T1 relaxation and homonuclear and heteronuclear NOE relaxation) can give detailed structural information. The ¹⁹F CSA mechanism is an important relaxation mechanism at high magnetic fields and several novel experiments have been designed, to determine the complete ¹⁹F CSA tensor. Several groups are also trying to apply ¹⁹F NMR techniques to study membrane proteins and intrinsically disordered proteins which have a fluorinated tag. This chapter will focus on novel NMR techniques using fluorine as a probe and their application to structure determination and conformational dynamics of fluorinated biomolecules.

Keywords: Biomolecular conformation, Biomolecular dynamics, Fluorinated amino acids, Fluorine spin, Multidimensional NMR.