Properties and Descriptors influenced by Tautomers

tautomers.md

Properties and Descriptors influenced by Tautomers

(non-exhaustive list)

(Thoughts resulting from previous discussions (6374, 6543))

(Please also have a look again at Roger's talk from last year's UGM (direct link to PDF))

Identity / Similarity

• InChIKey / SMILES (-> identity determination)
• Fingerprints (-> similarity determination, substructure matching, model training)

Scores & Descriptors (-> Model Training)

• QED
• NP Likeness
• LogP
• pKa (not calcuable by RDKit)
• PolarSurfaceArea (TPSA)
• ...

In addition to this list, everything depending on 2D/3D coordinates (e.g. docking) is influenced by tautomerism.

Goals of Canonical Tautomer Generation

1. Consistency
2. "Correctness"
   This ofc depends on multiple factors (solvent, pH, ...),
   but a certain level of (intuitive) "correctness" should be aimed for (avoiding the "Will I be getting yelled at?" effect).

Summary

• Canonical tautomers are probably much more important for your analyzes than you thought (at least this was the case for me)
• Important to always standardize / canonicalize your input structures
  • Esp. when different sources are used
• There are two modules to generate tautomers in the RDKit
  (and they give different results):
  • Chem.MolStandardize.tautomer.TautomerCanonicalizer (older implementation)
  • Chem.MolStandardize.rdMolStandardize.TautomerEnumerator (newer implementation)
• For some applications, tautomer enumeration might be a solution

How is Everybody Doing It?