Accurate, physics-based modeling of the aqueous ionization and speciation behavior of small molecules

Highly accurate Macro-pKa prediction for small molecules

Macro-pKa  is an automated solution for predicting macroscopic pKa values and pH-dependent tautomeric populations of ligands that combines physics-based DFT calculations with empirical corrections.

  • Automatically identify protonatable/deprotonatable sites, enumerate the protonation states, and calculate the micro-pKa values with an enhanced scheme for generating empirical corrections 
  • Calculate the complex aqueous speciation behavior of tautomerizable ligands
  • Capture nuanced but important energetic effects like conformational averaging, solvation/shielding, hydrogen bonding, and stereochemistry
  • Generate an easy-to-read report that includes predicted macro-pKa of a small molecule, its different constituent protonation states and their populations, and a speciation diagram for the major species in solution

Related Applications & Products

  • Jaguar 
  • Jaguar pKa applies DFT and empirical corrections to estimate the microscopic pKa values of non-tautomerizable small molecules
  • Epik enables rapid, empirical prediction of microscopic and macroscopic pKa values of small molecules


Read the science article


Report populations of pseudo-stereoisomers of non-symmetric tertiary amines

Citations and Acknowledgements

Schrödinger Release 2023-2: Macro-pKa, Schrödinger, LLC, New York, NY, 2023.

ö Discovery of a Novel Class of D-Amino Acid Oxidase Inhibitors Using the Schrödinger Computational Platform. J. Med. Chem. 2022, 65, 9, 6775–6802. 

· "Discovery of a Novel Class of d-Amino Acid Oxidase Inhibitors Using the Schrödinger Computational Platform"

Haifeng Tang, et al., Journal of Medicinal Chemistry, 2022, 65(9), 6775-6802
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