Allosteric Inhibitors of Enzymes
Ava Sih-Yu Chen
In this project, we will use structural bioinformatics to search protein crystal structures in the PDB for interactions that will allow us to identify novel allosteric inhibitors. We will identify the best structures and substructures to use as probes and design software to identify biologically relevant interaction sites between the probes and enzymes. We will use the same approach to identify chemical structures that can modulate protein-protein interactions and signalling, as well as novel druggable sites on known protein targets.
Having identified relevant chemical substructures, we will synthesise and assay series of molecules containing them, in order to experimentally develop structure activity relationships. We expect this to lead to promising new leads for drug design, and to series of molecules outside existing patent spaces.
Our results so far, involve using a scoring function RF-score to evaluate the protein-ligand interactions. And we also have implemented an algorithm for large scale classification of the interface between the ligand and the protein in protein-ligand complexes. We have used both methods in order to identify binding sites of a potential serendipitous binder for identifying the allosteric site.