Map PAINS substructures according to PAINS class and find the highest PAINS violation

Many scientists are unaware that PAINS substructures are classified by hit frequency; this has led to a tendency to irresponsibly use PAINS filters during compound triage by filtering out potential leads based on the presence of a PAINS substructure instead of the presence of a type of PAINS substructure. Baell suggested in his review, Seven Year Itch: Pan-Assay Interference Compounds (PAINS) in 2017 - Utility and Limitations, that scientists should focus on class A, maybe class B, and not class C. Because the original paper only reported hit frequency based on a singular assay technology, compounds should not be necessarily excluded for containing a class A substructure.

This protocol splits the different classes of PAINS into distinct substructure mapping subprotocols to produce a more informed PAINS report.

The SMARTS patterns can be obtained here.

This protocol is being made available in conjunction with an upcoming publication.