Carboxylic acid hits PositiveIon

[Evert-Homan]

Hi,

I have run a number of Pharmit queries and am occasionally seeing carboxylic acid groups hitting the PositiveIon feature, which doesn't make much sense imo. Query ligand with primary amine in magenta and hit with acid in cyan mapping the PositiveIon.

BW/Evert

[dkoes]

Are you sure that isn’t a positively charged nitro compound? https://en.wikipedia.org/wiki/Nitro_compound David Koes Associate Professor Computational & Systems Biology University of Pittsburgh On Mar 22, 2025, at 7:25 AM, Evert-Homan ***@***.***> wrote: Hi, I have run a number of Pharmit queries and am occasionally seeing carboxylic acid groups hitting the PositiveIon feature, which doesn't make much sense imo. Query ligand with primary amine in magenta and hit with acid in cyan mapping the PositiveIon. BW/Evert image.png (view on web)<https://github.com/user-attachments/assets/c8644c7b-1ec4-4326-b5c0-871192314540> — Reply to this email directly, view it on GitHub<#4>, or unsubscribe<https://github.com/notifications/unsubscribe-auth/AAR3Z7SCIHILIBFQLKXGSIT2VVCDBAVCNFSM6AAAAABZRZBJEGVHI2DSMVQWIX3LMV43ASLTON2WKOZSHE2DAMZSGA2DQMI>. You are receiving this because you are subscribed to this thread.Message ID: ***@***.***> [Evert-Homan]Evert-Homan created an issue (dkoes/pharmit#4)<#4> Hi, I have run a number of Pharmit queries and am occasionally seeing carboxylic acid groups hitting the PositiveIon feature, which doesn't make much sense imo. Query ligand with primary amine in magenta and hit with acid in cyan mapping the PositiveIon. BW/Evert image.png (view on web)<https://github.com/user-attachments/assets/c8644c7b-1ec4-4326-b5c0-871192314540> — Reply to this email directly, view it on GitHub<#4>, or unsubscribe<https://github.com/notifications/unsubscribe-auth/AAR3Z7SCIHILIBFQLKXGSIT2VVCDBAVCNFSM6AAAAABZRZBJEGVHI2DSMVQWIX3LMV43ASLTON2WKOZSHE2DAMZSGA2DQMI>. You are receiving this because you are subscribed to this thread.Message ID: ***@***.***>

[P4j45]

Ouch, my bad, it is nitro. But still should not hit PositiveIon imo.

[dkoes]

According to the SMARTS patterns we use to identify pharmacophore features, any atom with a positive formal charge will match a positive ion. While it certainly would be reasonable to exclude zwitterions, unfortunately we don't.

[P4j45]

Fair enough. It's not a problem for me because I will filter out any nitro containing hits later anyway.

BW/Evert

[dkoes]

Yup, that's part of the rationale for permissive definitions - easy enough to filter hits.