General descriptionTiPs has been developed with the aim of facilitating the identification of potential therapeutical targets in more than 150 organisms responsible for human infections. We performed a large-scale analysis to systematically identify candidate targets in the proteome of pathogen organisms. Predictions are made using the available information on drug-target three-dimensional (3D) complexes and by exploiting the homology relationships of known drug targets with pathogen proteins. Predicted pathogen targets are further annotated with sequence, structural and functional information. Users can quickly prioritise drug-target pairs by running simple queries (by organism, protein family or function, or UniProt ID), getting a list of candidate drug targets, and analysing the pattern of interactions between the pathogen proteins and the drugs predicted to target them.
Database searchThe database can be queried using one of the following options: Select your species of interest: You may choose an organism species (i.e.: Leishmania major) from a drop down menu. The query will return all database entries for that species. You can also retrieve predicted drug-target pairs for all the species available in the database by selecting the "*" wildcard. See example 1 Select your genus of interest: You may select an organism genus from a drop down menu. The query will return all drug-target predictions for the selected genus (i.e.: Leishmania). See example 2 Filter by (optional): Results can be filtered by any of the following criteria:
- protein_name (i.e. Calmodulin)
- pfam_code (i.e. PF00254)
- pfam_name (i.e. Urease_beta)
- ec_number (i.e. 2.7.1.-)
- go_number (i.e. 5524)
- go_description (i.e. ATP binding)
Example 1: Search for drug-target pairs in all pathogen organisms available in TiPs and filter by the "ATP binding" GO term. The search will return all drug-target pairs whose target is associated with the "ATP binding" GO term.
Example 2: Search for drug-target pairs in the Leishmania genus (i.e all Leishmania species) with no filter.
Example 3: Search for a specific protein of interest in the TiPs database. All drug-target pairs whose target has the G4VP62 UniProt AC will be returned.
Result tableThe output of any type of search is a table reporting exhaustive information about the known drug-target pairs and the predicted ones. The table has the following column headers:
- Drug name It is linked to the drug page (see below)
- Organism The name of the organism on which the drug is known to be effective
- Known target Uniprot ID of the known molecular target of the drug. It is linked to the protein page (see below)
- Predicted organism Name of the organism on which the drug is predicted to be effective
- Taxonomy ID Taxonomy identifier of the pathogen organism. It is linked to Taxonomy database
- Predicted target Uniprot ID of the predicted pathogen target. It is linked to the protein page (see below)
- Protein name Protein name of the predicted target
- BSI BLAST global Sequence Identity between known and predicted targets
- BSSI is the Binding Site Sequence Identity between known and predicted target binding sites calculated as the precentage of identical residues over the aligned residues in the binding site
- BS RMSD Binding Site RMSD calculated after local superposition of the C-alpha atoms of known and predicted binding site residues. When the structure of the predicted target is experimentally solved, the best resolution one is used for the superposition.
- Clashes indicates the presence/absence of atomic clashes beetween drug and protein atoms. Clashes can involve side chain atoms (s.c.) or main chain atoms (m.c.)
- Indels indicates the presence/absence of indels within 5 Angstroms from any atom of the drug
- 3D complex It is linked to the structure page (see below) where the user can analyse and/or download the structure of the predicted drug-target complex. When the drug-target complex has experimantally solved structure(s) it provides a link to the PDB page