The Jaguar pK_a Prediction Module

Schrödinger’s pK_a prediction module was one of the first ab initio quantum-chemical methods to reliably predict pK_a values in aqueous media [258]. The module uses a combination of correlated ab initio quantum chemistry, a self-consistent reaction field (SCRF) continuum treatment of solvation, and empirical corrections to repair deficiencies in both the ab initio and continuum solvation models. This combination leads to high accuracy for a wide range of organic compounds, in conjunction with tractable computational requirements.

A workflow has been designed that manages running the many individual jobs required to assemble the various components of the calculation. Each of the components has been optimized for the best tradeoffs of accuracy versus efficiency. The empirical correction terms, which have been developed for ionizable groups relevant to the chemical and pharmaceutical industries, are specifically designed to work with the basis sets, electron correlation levels, and solvation model of the ab initio methodology. The transferability of the corrections has been tested by examining a sizeable set of test molecules.

For information on setting up a calculation from Maestro, see Jaguar pKa Calculations. You can also edit the Jaguar input files for a pK_a calculation—see Jaguar Input Files for pKa Calculations. For a tutorial exercise, see pKa Predictions with Jaguar pKa.

The topics listed below cover various aspects of the theory and implementation of pK_a calculations in Jaguar.