We are looking for an outstanding, highly motivated Postdoctoral fellow to join the Thornton group at the European Bioinformatics Institute (EMBL-EBI) located on the Wellcome Trust Genome Campus near Cambridge in the UK.
One of the Thornton Group's collaborations is a consortium called the Midwest Center for Structural Genomics (MCSG, http://www.mcsg.anl.gov). This comprises 7 groups located in the US, UK and Canada and focuses on high-throughput structure determination of proteins of biological interest - particularly those relevant to tackling human disease.
As part of the consortium, the Group has developed a number of computational tools to assist crystallographers and biologists, both within the consortium and elsewhere. The most recent tool is a web server called LigSearch (http://www.ebi.ac.uk/thornton-srv/databases/LigSearch) which aims to identify small molecules that are likely to bind to a given protein. The server takes the protein sequence and searches various databases, including ChEMBL and the PDB, to provide a ranked list of likely binders. Its purpose is to help crystallographers preparing to solve the 3D structure of a new protein identify which small molecules are worth trying. A protein-ligand complex often provides valuable biological information on the protein's natural binding site and the ligand interactions it makes.
There will be scope for the successful candidate for improving and expanding the server. At present, the system uses only the protein sequence, but in cases where the structure is known this might provide a richer and more reliable source of information on binding compounds. Secondly, a more chemistry-aware filter of the output is required to eliminate volatile compounds. Third, the hits need to be screened against a database of commercially available molecules, such as ZINC, to indicate which are readily purchasable and their cost. The system might also have applications in related areas, and further research is needed in collaboration with experimental groups to assess the quality of the system's results. Some improvements to the current system to make it more robust will also need to be made. A small part of the work will involve using the ProFunc program (http://www.ebi.ac.uk/thornton-srv/database/profunc to functionally annotate new MCSG structures.