#11thICCS Peter Pogany - Fast molecular searching tools and their extension at GSK
Search tools at GSK: Uses MadFast from Chemaxon; SmallWorld from NextMove; FFSS from GSK; Fraggle from GSK
Reduced graphs represented as SMILES where particular features are represented using unusual elements, e.g. [Sc] for aromatic.
The reduced graph fp is useful for pharmacophoric search. Attachment points are largely ignored, for example.
Describes use of edit distance to measure chemical similarity, with SmallWorld from @nmsoftware. Then Fraggle search via fragmentation and then Tversky search - also requires postprocessing.
Why performance matters. We cluster the whole screening collection (>2M) every weekend. Highly parallelisable. Similarity and clustering is the rate limiting step in cmpd acquisition. Real time search is neccessary.
Dbs are getting bigger quickly. ZINC and Enamine REAL. Need to know if dev cmpds are in these databases as can't patent them if so.
MadFast stores fps in memory and so is faster. Do an all against all similarity calc every weekend for sphere exclusion clustering.
Overlap calculations uses InChIKeys. This caused problems due to hash collision, and are moving to SMILES (?)
Get data from SureChEMBL. Data available with days of patent becoming available.
Q: DB sizes not increasing linearly, but more than that. What will do? A: We're okay for now (up to 3/4 billion) but might be a problem later.
