deletions | additions       diff --git a/section_Example_To_demonstrate_Pharmit__.tex b/section_Example_To_demonstrate_Pharmit__.tex  index 3695e18..91ef078 100644  --- a/section_Example_To_demonstrate_Pharmit__.tex  +++ b/section_Example_To_demonstrate_Pharmit__.tex 
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Pharmit identifies 26 pharmacophore features in ANP, 14 of which are interacting with the receptor. Searching with this default query yields no hits as it is overly specific. In general, we find that queries rarely benefit from having more than 5 distinct features.  To generate a useful query for 2SRC, we rationally target the canonical hinge site, with which ANP strongly interacts, by including a hydrogen donor and acceptor and an aromatic ring to mimic the adenine moiety. Searching with this reduced query produces 92,398 hits (matching conformations) with an EF of 2.8. Adding a directionality constraint to the aromatic ring reduces the number of hits by 2,000 and slightly increases the EF. The user can then interactively explore adding additional interacting features to the query. The addition of a hydrogen acceptor interaction on the ribose of the ligand, as shown in Figure~\ref{}, generates 1,881 hits with an EF of 16.8. The addition of an exclusive shape constraint with a tolerance of 2.5, which filters out compounds with severe steric clashes with the receptor, decreases the number of hits to 1,248 and increases the EF to 18.4. Alternative queries can yield even higher enrichment factors at the expense of lower F1 scores due to fewer total active compounds being returned. In this case the user is guided by a benchmark library, but a similar interactive exploration is possible through rational investigation of the hit compounds of query.    Query results can be minimized to produce a more meaningful ranking, as shown in Figure~\ref{}, where the top 13 compounds, and 16 of the top 20, are correctly identified actives. An offline analysis    We anchor the query at the other side of the pocket by including a hydrogen acceptor, for a total of five features. While this query is reasonable given the structure of the kinase, strong interactions with functional groups in the pocket are possible outside of the narrow constraints derived from the small donor/acceptor tolerance spheres; as it is, few hits are returned. Thus the tolerance spheres for donors and acceptors are increased to 1.0. Finally, several features included in the query are likely interacting with a single group in the pocket, making it reasonable to impose a directionality on these features. The hydrogen acceptor interacting at the hinge site is given a $\phi$ of 90 and $\psi$ of 45, and the second aromatic is given a $\phi$ of 10 and $\psi$ of -50. The DUDe 2SRC benchmark set, which consists of small molecules known to bind 2SRC as well as structurally similar compounds that do not bind, is a contributed library available to search within Pharmit, and this is used to validate the pharmacophore. Searching generates 39 hits, with an enrichment factor of 41.1.