A PhD student position is available to develop new protein modelling methods which can be applied to drug design. The successful candidate will work in collaboration with the Blundell and Hyvonen groups in the Cambridge University Biochemistry Department and industrial CASE award sponsors Eli Lilly.
The optimization of a lead molecule in the early drug discovery process is greatly accelerated by knowledge of the protein-ligand binding mode. However it is not always possible to reliably predict this binding mode starting from crystal structures of related proteins and ligands, due to the conformational flexibility of the binding site. Inferring binding mode becomes particularly hard for systems like GPCRs where there are substantial difficulties in obtaining experimental protein-ligand structures. The project will aim to develop a methodology for predicting binding modes by combining approximate structural knowledge of the target with available ligand activity data. The chosen student will work to extend the Rapper program to use ligand-based pharmacophores as restraints in generating feasible protein conformations, and to validate results on experimental data. Applications should include a covering letter describing relevant research experience to date, a CV, and the names and addresses of two referees. These should be sent to Dr Mako Hyvonen (marko -at- cryst.bioc.cam.ac.uk) by email by 10th February 2009. Paper copies cannot be accepted. This studentship is open to EU nationals only. Limit of tenure: up to 3 years in first instance. See also : http://www.jobs.ac.uk/jobs/ZL434/Computational_Structural_Biology_--_CASE_PhD_Studentship/ ----Sent on behalf of Prof Tom Blundell and Dr Marko Hyvonen----
