2023-24-project-catalogue

###Exploring high-order multiple-quantum coherences for the characterisation of molecular dynamics by ultra-high field NMR

Project ID: 2228bd1103 (You will need this ID for your application)

Research Theme: Physical Sciences

UCL Lead department: School of Pharmacy

Department Website

Lead Supervisor: Chris Waudby

Project Summary:

NMR spectroscopy is a vital tool for the characterisation of molecular interactions and conformational dynamics. With the advent of ultra-high field spectrometers (with a national EPSRC-funded 1.2 GHz spectrometer expected to come online in the UK during this studentship), there is a pressing need to develop experimental methods that fully exploit the capabilities of these new systems.

This project will explore field-dependent NMR measurements of multiple-quantum relaxation for the analysis of chemical exchange in supramolecular complexes and isotopically labelled and unlabelled biomolecules. Prior work in the group has discovered the existence of slow-relaxing quadruple-quantum coherences within methyl spin systems, and has shown that field-dependent Hahn echo measurements of their relaxation rates can provide a sensitive probe of chemical exchange (Waudby et al., Magn Reson 2021). This project aims to develop these findings in a number of directions, to be adapted as the project evolves and in response to the student’s own interests. This includes exploring quadruple-quantum CPMG relaxation dispersion experiments; developing perfect echo experiments for application to supramolecular systems, host-guest recognition, and unlabelled biomolecules; and developing easy-to-use software for the statistically-rigorous analysis of these experimental results.

Although expected to be of general utility, these new methods will be applied particularly to characterise conformational flexibility in antimicrobial peptides in collaboration with the Dickman group (second supervisor). Flexibility in membrane-active peptides is often essential for their pore-forming behaviour, so understanding how structural changes affect peptide dynamics can help us rationalise observed changes in pore-forming activity.

This project would appeal to candidates with a strong background in physical chemistry. Experience with coding would be an advantage, but full training will be provided. The student will also be trained in NMR theory and methods, together with quantitative skills, particularly mathematics, computational data analysis and software engineering using the state-of-the-art high-level, high-performance Julia language.