Scripted testing for aggregators

To script testing for aggregators, you have two options, aggregator advisor and ZINC15.

Aggregator advisor

• Download the python script simi.py which may be found at http://advisor.bkslab.org/faq/#Command.

Prepare your molecules to be tested. Here we test the first 100 FDA approved compounds from ZINC

wget zinc15.docking.org/substances/subsets/fda.smi

The file looks like this

$ grep -n  ZINC000000020237 fda.smi  
32:CCN(CC)CC(=O)Nc1c(C)cccc1C ZINC000000020237

• Run the program as

python simi.py  similar fda.smi > output

• When there are matches to aggregators, each line contains :
  • original smiles
  • matched aggregator
  • tanimoto similarity (in the paper we suggest 0.85 cutoff, but we are more generous in the calculation here to allow you to make the cut
  • original identifier from the input file
• e.g. the first line of output is as follows

$ python simi.py  similar fda.smi
CCN(CC)CC(=O)Nc1c(C)cccc1C	Cc1cccc(C)c1NC(=O)CNc1ccccc1	 0.87	ZINC000000020237

ZINC15

We now have a bulk processing facility, the right hand side of http://zinc15.docking.org/patterns/home/. It supports both PAINS and Aggregator similarity searches.

To use it, paste SMILES, one per line, or upload a file, up to 1000 per transaction. A whitespace-separated identifier after the SMILES is optional. It can be used with curl programmatically if you prefer.

For instance, if you enter: CCOc1ccc([C@@H]2[C@H]3CCCC=C3C(C#N)=C(N)C2(C#N)C#N)cc1 some_identifier

and click on "Check" you will see it matches: cyano_ene_amine_A(56)

If you enter: C1=CC(=C(C=C1C2=C(C(=O)C3=C(C=C(C=C3O2)O)O)O)O)OC blah_blah_blah

and click on "Check" you will see it is similar to an aggregator, and we have a button that allows you to run it again in the Aggregator Advisor as published recently in J Med Chem. We've used ECFP4 Tc 0.6 instead of axonpath 0.85 as in the paper, so it is an approximation. 0.55 ECPF4 might be better, we're still testing.

There is a way to script this. It is similar to but not exactly the same as the aggregator advisor. If you want the scripted version, please write me.

curl http://zincfifteen.docking.org/patterns/apps/checker.txt -F upload=@smiles_file -F pains=y -F aggregators=y

please do not over use this feature. Slow! works best with < 100 smiles per transactions

-- John