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Accurate pKa prediction and automatic structure modification is critical for many computational chemistry methods which are strongly dependent on the tautomerization and protonation state of the structures, including docking, binding affinity estimation, QSAR and ADME modelling, and metabolism prediction.

MoKa implements a novel approach [1] for in-silico computation of pKa values; trained using a very diverse set of more than 25000 pKa values, it provides accurate and fast calculations using an algorithm based on descriptors derived from GRID molecular interaction fields.

Key Features:

  • accurate: prediction error of 0.4 log units (0.7 for novel structures)
  • fast: more than one million predictions per hour
  • automatic: output top N most abundant species at a designated pH
  • self-trainable: incorporate additional experimental data to improve accuracy

MoKa 3.0 enhancements

  • The number of models describing the chemical space has been expanded from 53 to 56.
  • The internal database of experimental values has been expanded to 26000 compunds
  • Hundreds of molecules have been synthesized and experimentally tested to improve the training of a number of prediction models
  • Tautomer enumeration is now exhaustive, and also independent of the input tautomer.
  • Cheto-enol tautomerization forms has been improved
  • Redundant protomer enumeration is now allowed as an optional argument, so that both protonation states are produced when there are two ionization states with a close predicted pKa difference
  • Model training via Kibitzer has been improved significantly, and the analysis of experimental versus predicted has been incorporated into Kibitzer

Package content

Graphical interface for predictions

  • tautomer check
  • batch mode for multi-structure files
  • integrated structure editor
  • cut & paste from ISIS/Draw (Windows version)

System training module

  • independent GUI for system training
  • automatic assignment of exp. pKa values to ionization sites
  • building of customized pKa prediction models to load into MoKa

Command line tools

  • MoKa command line

    • easy integration with existing tools
  • Generation of ionization states of a compound

    • single ionization state mode at user-specified pH value
    • multiple ionization states mode at user-specified pH value or pH range
  • Tautomers enumeration and stability estimation [2]

    • batch enumeration of tautomers and estimation of tautomer stability


MoKa is available for Windows® and Linux® operating systems.

Editions comparison

MoKa comes in two editions: Solo and Suite

MoKa-Solo provides an interactive interface for pKa investigation for 1 or more CPU; Moka-Suite provides unlimited (site-wide) interface access and also command-line utilities for wider enterprise deployment in cheminformatics processes.

This matrix provides an overview of what is provided by the different editions.

  Solo Edition Suite Edition
Graphical interface for predictions yes yes
Automatic comparisons with experimental data yes yes
Command line batch predictions no yes
Generation of ionization states of a compound no yes
Tautomers enumeration and stability estimation no yes
System training module no yes


[1] New and Original pKa Prediction Method Using Grid Molecular Interaction Fields
Francesca Milletti, Loriano Storchi, Gianluca Sforna, and Gabriele Cruciani
J. Chem. Inf. Model., 2007, 47 (6), pp 2172-2181

[2] Tautomer Enumeration and Stability Prediction for Virtual Screening on Large Chemical Databases
Francesca Milletti, Loriano Storchi, Gianluca Sforna, Simon Cross and Gabriele Cruciani
J. Chem. Inf. Model., 2009, 49 (1), pp 68–75

[3] Tautomer Preference in PDB Complexes and its Impact on Structure-Based Drug Discovery
Francesca Milletti and Anna Vulpetti
J. Chem. Inf. Model., 2010, 50 (6), pp 1062–1074