Hello to all,
After having some communications with the ChemAxon support team about details regarding the pKa algorithm, it would be a good idea to make the questions public. So, here goes - hope you can answer them!
Which partial-charge algorithm did you use? It wouldn’t be
Gasteiger-Marsili by any chance, if not an in-house ChemAxon algorithm?
Same for polarisabililty – how did you calculate it?
What are “structure-specific” increments and how do you define
ionisable sites? A ChemAxon poster mentioned some simple definitions of acidic
and basic groups, but are these actually used in the regression model?
Surely if it’s site-specific then you’d need to take into account the
functional group (as well as surrounding atoms to account for steric effects)?
What sort of compounds did you train the regression model
How does this relate to cxtrain when a “local model” is
trained? This is very important as we have several unique chemical series
which one won’t find in public datasets.
In addition, do
you have any published (or private) examples of cxtrain-pKa being used? My experience on our
compounds showed little benefit, but I also think that I didn’t use cxtrain
properly, yet I've found no evidence in the literature (yet) that shows cxtrain being used for pKa. Seeing as it’s a regression model based on descriptors as
well-respected as partial charges, I find it somewhat hard to believe that
training did not work in our case...
Thanks in advance,