Introduction to Epik Classic

Epik Classic is a program for the prediction of the pK_a values of the ionizable groups in ligands, and for the generation of the probable ionized and tautomerized structures within a given pH range. Epik Classic rapidly and consistently predicts pK_a values, employing the widely used and respected Hammett and Taft empirical equations. The values of the parameters in these equations are determined from fits to experimental data either from the literature or from Schrödinger’s own development efforts. Epik Classic employs extensions to Hammett and Taft technology for handling mesomers, including standardization of mesomeric forms and charge spreading. Tautomer probabilities are estimated using a database of tautomerizations derived from experiment and quantum chemical calculations. Both the ionization and tautomerization employ user-modifiable databases of parameters. Collections of probable structures are generated by iteratively tautomerizing and ionizing the base structure. In addition, Epik Classic can be used to generate structures suitable for studies involving metalloproteins.

Since Epik Classic is fast, and yet has a range of options, it is suitable for processing large collections of input structures for a variety of purposes. Epik Classic may also be used by Schrödinger’s ligand preparation product, LigPrep, instead of the ionizer and tautomerizer found in LigPrep. Epik Classic may be run from Maestro or from the command line.

Epik Classic’s structure generation mode estimates state penalties which reflect the predicted populations in solution for the structures it generates. These penalties can be used in the scoring of poses in Glide docking calculations to obtain better enrichment.

If you publish work that uses Epik Classic, please cite Epik Classic as indicated on our citation page.