pKa - big differences in pKa values with different options

Dear all,

We have experienced several times, that pKa-Values differ a lot depending on the settingof some options (e.g. "Take major tautomeric form"). The values differ significantly even in parts of the molecule not affected by tautomerism. Furthermore, we have experienced significant differences between calculated pKa's in different versions of the plugins (specifically between 5.2.5.1 and 5.3.5 which we currently use).

Three Questions:

- Is there additional documentation available describing the algorithm used to calculate pKa's?

- Is there additional documentation available explaining the effect of the various settings?

- Is there additional documentation avialable explaining the changes in the algorithm between versions, specifically between the ones mentioned above?

Thank you very much for your help!

Adrian

Dear Adrian,

have you checked the plugin's documentation? Please find information on the pages:

http://www.chemaxon.com/marvin/help/calculations/protonation.html#pka

http://www.chemaxon.com/marvin/help/calculations/pKa.html

http://www.chemaxon.com/marvin/help/calculations/redbluepka.html

 

As our team is developping the calculation methods (by using for example a larger set of molecules and their pKa data), results may differ from version to version.

Hi,

 

I found one more reference which is relevant  to the pKa algorithm.

https://www.chemaxon.com/conf/Calculating_pKa_values_of_small_and_large_molecules.pdf

The tautomer generation changed beetwen the versions (5.2.5 and 5.3.5)  and a bug releated with hydrogenization was fixed. 

A little modification in a molceule ususally can not result in significant change in the calculated pKa. Please let us known if you encounter such kind of an unexpected (abrupt) change in the calculated pKa. It may be a bug.

 

Changes of the released versions are collected at this site.

http://www.chemaxon.com/marvin/help/developer/changes.html

 

Jozsi