Developing Cholinesterase (AChE) inhibitor screening methods using Nuclear Magnetic Resonance Spectroscopy (NMR)

This EPSRC CASE studentship awarded to the University of Kent, in association with DSTL, will develop NMR-based screening methods to obtain binding affinities and specific binding mode analyses of key compounds, including organophosphates, to human AChE. AChE is primarily located in neuromuscular junctions, neural synapses and on red blood cell membranes and is from the family of cholinesterase enzymes that catalyse the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid.

Key aims of the project are to understand the molecular processes driven by inhibitors of human AChE to facilitate the design process of preventative agents to these chemicals. Skills to be gained include NMR spectroscopy, bioinformatics enzyme biochemistry and biophysical protein characterisation. The primary driver will be the development of specific NMR approaches to study ligand-protein binding modes and affinities that enlighten our understanding of AChE inhibitors.

Project supervision will be provided by Dr. Mark Howard (Kent) and Dr. James Jones (DSTL). The project partners have international-level expertise in bioinformatics, protein expression, purification and characterisation in addition to a world-leading competence in the use of NMR spectroscopy in characterising protein-ligand interactions. In addition to researching an area of extreme biological and biomedical interest regarding AChE, this also will train the successful application in advanced biological and industrial NMR spectroscopy.