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Dr Joel Loveridge 


I am interested in the relationship between the structure, dynamics and function of enzymes, as a route to understanding and controlling nature’s chemistry. This work involves multidimensional NMR spectroscopy in conjunction with other biophysical techniques. Cardiff’s flagship 600 MHz Bruker NMR spectrometer is equipped with a quadruple resonance QCI cryoprobe capable of simultaneous pulsing and decoupling on 1H, 13C, 15N and 31P, making it ideal for studies of proteins, nucleic acids and their complexes, as well as small molecules. The ability to switch the 1H channel to 19F further extends its utility to include fluorine-labelled biomolecules or xenobiotics. Current projects include:

Dihydrofolate reductase and the physical basis of enzyme catalysis

There is a great deal of controversy surrounding whether protein motions may couple directly to the chemical step of an enzymatic catalytic cycle. In collaboration with Prof. Rudolf Allemann, this work studies the effects of organic cosolvents on the structure and dynamics of the model enzyme dihydrofolate reductase, and investigates the dynamics of the bound ligands. By relating these results to kinetic data published previously, we hope to distinguish between models in which protein motions are coupled to those of the bound ligands in a manner which directly affects the rate constants of the reaction and models in which conformational effects are important for setting the correct environment for reaction but which play an otherwise passive role the chemistry itself.

Photoactive DNA binding proteins

This work seeks to understand structural and dynamic effects in a novel class of DNA binding proteins that are active only after irradiation with blue light. The switchable nature of these proteins provides an extra dimension to separate dynamics which are involved in DNA binding, those which are involved in the switching process, and those which are important for neither. This work also provides an opportunity to develop novel photoswitchable proteins with a range of activities on DNA.

NMR studies of challenging targets

Conventional NMR techniques are only readily applicable to relatively small proteins, due to the combined problems of excessive spectral overlap preventing unambiguous assignment and reduced tumbling rates leading to faster transverse relaxation in larger proteins. However, non-conventional techniques such as unusual labelling patterns and NMR methods can be used to at least partially overcome these problems and so provide structural information on these challenging targets. NMR can also be used in conjunction with crystallography to provide complementary (particularly dynamic) information without the need to assign resonances for the entire protein.