The Advantages of Empirical pKa Prediction
Proper treatment of ligand protonation states is essential to lead discovery. The pKa's of a drug's various functional groups play a critical role in determining its bioavailability and pharmacokinetic profile, while virtual screening software relies on correctly protonated structures in order to perceive the discrete interactions that drive ligand binding. However, many readily available libraries provide ligand structures in familiar tautomeric forms with all functional groups neutralized. These forms may not be highly populated under biological conditions, and are therefore inappropriate for property prediction or virtual screening experiments.
Epik provides a time-tested solution to these problems, designed specifically to work within the context of contemporary drug discovery workflows. Using Hammett and Taft methods in conjunction with ionization and tautomerization tools, Epik is able to rapidly and reliably predict pKa values and return all chemically sensible structures.