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jensengroup / propka

PROPKA predicts the pKa values of ionizable groups in proteins and protein-ligand complexes based in the 3D structure.
http://propka.org
GNU Lesser General Public License v2.1
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unexpected ligand pka values #143

Open mbatgh opened 2 years ago

mbatgh commented 2 years ago

Hi,

I just used propka3 (as downloaded and installed from github) to analyze a few structures from the PDB. I used the "-o 7" command line option, and other than that, all defaults. The results look in most cases as expected, but I have three cases were the results for bound ligands are very unexpected. these are: 7JTO, 7JTP, 6W8I (the output .pka files from propka are attached) what I see is: 7JTO: I get pka=10.66 for a ligand nitrogen (chain B res VKA N65) which is directly bound to an aromatic ring 7JTP: as above for X6M N1, also there is one more piperazine N (chain A res X6M N) which propka seems to ignore. 6W8I: chain D res TKY N50, pka = 9.65 - this is an amide nitrogen

If I understood this correctly then, at pH~7, all the nitrogens mentioned aboved should be protonated/charged according to propka, which I cannot see happening for these compounds. Please let me know in case I overlooked/misunderstood something here!

thanks, Michael

pkaoutputs.zip

jhjensen2 commented 2 years ago

For some reason the code is assigning the wrong atom type to these Ns. For example for 6W8I N50 is assigned to be a tertiary N (N33), but should be an amide (NAM) and thus non-tritrateable.

So these problems appear to be due to bugs in the code. I am no longer active on PropKa, but perhaps someone can look into this?

mbatgh commented 2 years ago

Thanks for the reply ... I take it the relevant code is supposed to be in: ligand.py I was, in fact surprised, that propka tries to infer atom types/bond orders, etc from PDB input alone, as this is rather difficult and error prone, is there a way to supply an sdf or mol2 file instead of relying on the PDB?