The druggability index query lets you restrict your search based on a druggability measure.
The druggability index (Dindex) is a composite score consisting of a weighted normalised sum, where each of the different druggability prediction methods are given different weights depending on their relative contribution to prediction. The Dindex values range from 0 to 1, where a larger index score means a more likely to be druggable target. A description of this analysis is provided in "Al-Lazikani B, Gaulton A, Paolini G, Lanfear J, Overington J and Hopkins A (2007). The molecular basis of predicting druggability; in Bioinformatics, from Genomes to Therapies, Vol 3. Edited by Thomas Lengauer, Wiley-VCH"
In cases where the information about druggability is not available from the pathogen protein itself, it is derived from the closest druggable homolog, and the degree of similarity and conservation of essential motifs and features is used to adjust the final dindex. Known druggable targets were derived from the Inpharmatica literature SAR database (Starlite)
The similarity vs druggable targets query lets you restrict your target searches to those that have a positive hit (using BLAST) against the Starlite database of known targets.
Do note that this filter and the Dindex filter are redundant. The Dindex calculation already includes a similarity component. This filter is mainly provided for new genomes in TDR Targets (S. mansoni) that were not yet submitted for Dindex calculation.
The compound desirability query lets you restrict your search to targets based on the chemical quality of the compounds associated with the target (or with its closest druggable homolog).
The compound desirability index (Pfizer) was calculated for the compounds associated with each of the closest druggable targets (as measured by BLAST similarity, see above). The compound desirability index is a fitness value that summarises the average `chemical quality' of each target.
The compound desirability value links direct to actual compounds (which could the basis for composing target-specific screening subsets of compounds), but these have not been disclosed and are not available for searching and/or display.
The desirability function is based on Harrington's desirability index where the target function is based on the molecular properties distribution of oral, small molecule drugs. The function also contains penalty functions for acticity, promiscuity and structural alerts (risk and reactive groups in compounds).
Associated compounds: associations between genes and chemical compounds are derived from a number of sources. In each case the association between a gene and a compound has been done by different methods, and thus the reliability and/or the relevance of the association is different for each source.
The sources are: i) manual curation (more reliable, more relevant); ii) transitive (semi-automatic) association of compounds to gene A based on its similarity to a gene B for which there are known compounds (DrugBank); iii) finally associations between compounds and enzymes have been established based on co-occurrence of EC numbers and compound identifiers (CAS registry IDs) in PubMed abstracts (indexed for MEDLINE). In this last case because the link between the gene and the compound is established only due to co-occurrence, there is no guarantee of any functional
association between the targets and the associated compounds. In other words, there is no guarantee that genes annotated with an EC number will interact, bind to, or be inhibited by the compounds that are mentioned in the corresponding papers. Also, the compounds obtained in this way might not be the same as those for which the desirability index has been calculated. You have been warned.