Abstract:
BACKGROUND: Drug resistance to anti-malarial compounds remains a serious problem, with resistance to newer
pharmaceuticals developing at an alarming rate. The development of new anti-malarials remains a priority, and the
rational selection of putative targets is a key element of this process. Discovery-2 is an update of the original
Discovery in silico resource for the rational selection of putative drug target proteins, enabling researchers to obtain
information for a protein which may be useful for the selection of putative drug targets, and to perform advanced
filtering of proteins encoded by the malaria genome based on a series of molecular properties.
METHODS: An updated in silico resource has been developed where researchers are able to mine information on
malaria proteins and predicted ligands, as well as perform comparisons to the human and mosquito host
characteristics. Protein properties used include: domains, motifs, EC numbers, GO terms, orthologs, protein-protein
interactions, protein-ligand interactions. Newly added features include drugability measures from ChEMBL,
automated literature relations and links to clinical trial information. Searching by chemical structure is also available.
RESULTS: The updated functionality of the Discovery-2 resource is presented, together with a detailed case study of
the Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase (PfSAHH) protein. A short example of a chemical
search with pyrimethamine is also illustrated.
CONCLUSION: The updated Discovery-2 resource allows researchers to obtain detailed properties of proteins from
the malaria genome, which may be of interest in the target selection process, and to perform advanced filtering
and selection of proteins based on a relevant range of molecular characteristics.
