Abstract

NMR spectroscopy provides a powerful approach for the characterisation of molecular interactions by analysis of experiments acquired over the course of a titration measurement. Such data are rich in structural, mechanistic, thermodynamic and kinetic information, which can be extracted through the quantitative analysis of resonance lineshapes. This talk will review our recent progress in developing a rigorous theoretical framework for the analysis of NMR titration data [1-3], which eliminates systematic errors associated with previous ad hoc approaches and provides improved sensitivity to detect and analyse more complex multi-state interaction mechanisms such as induced fit or conformational selection. We will demonstrate the implementation of our new approach in a simple software tool, NMR TITAN [4], illustrated with a range of examples including 19F-detected NMR, and simple or multi-state protein-ligand and protein-protein interactions. [1] Waudby CA, Ramos A, Cabrita LD, Christodoulou J. Sci Rep 6 24826 (2016). Two-Dimensional NMR Lineshape Analysis. [2] Waudby CA, Frenkiel T, Christodoulou J. Angew Chemie Int Ed 131 8876-8880 (2019). Cross-peaks in simple two-dimensional NMR experiments from chemical exchange of transverse magnetization. [3] Waudby CA, Ouvry M, Davis B, Christodoulou J. J Biomol NMR (2020). https://doi.org/10.1007/s10858-019-00297-7. Two-dimensional NMR lineshape analysis of single, multiple, zero and double quantum correlation experiments.