£31,656 – £35,609 per annum (Grade I) £35,609 – £40,082 per annum (Grade J)
The main purpose of this role is to use computational molecular simulation and modelling methods to explore ligand binding and activity within well-defined nictotinic acetylcholine receptor environments, in collaboration with experiments. The overall aim is to understand partial agonism of these receptors and to design potential lead molecules for smoking cessation. New homology models of the human nAchR subtypes will be built and used to predict ligand binding modes and affinities and to assess and rationalise subsequent receptor activation. Starting from cytisine, modified ligands will be designed to enable/exploit new binding motifs within the variable -subunit (based on our earlier structural data) and probe the nature of the (pyridone) H-bond acceptor and role of a “bridging water” in ligand recognition. Models of the complete receptor extracellular domain together with new (and existing) biological and further structural data acquired during the project will allow definition of the mechanism (ligand-receptor interactions/protein response) of partial agonism in functionally important nicotinic receptors. Conformational changes associated with ligand binding, revealed by long molecular dynamics simulations, will be related to the trans-membrane channel open and closed states that have been studied previously by X-ray and EM structural studies. This position is to carry out research in molecular docking and simulation, under the supervision of Dr. Richard Sessions (Biochemistry) and Professor Adrian Mulholland (Chemistry) to analyze and present results, including preparing them for publication, and to liaise with researchers in synthetic chemistry (supervised by Professor Tim Gallagher, Chemistry) and other collaborators involved in the research project, including demonstrating computational molecular simulation methods.
The successful applicant will have a PhD in Biochemistry, Chemistry or related discipline.
Closing date for applications is midnight Wednesday 31 August 2016