Incorrect Standardizer Configuration Script?

Hi,

I wanted to standardize a set of molecules such that salts were considered duplicates and that all (de)protonated species were converted to their neutral form. I also wanted to aromatize the molecules.

In addition, as I eventually intend to compute descriptors for my data set (including those based upon substructures), and for a PubChem data set, I decided to incorporate the transformations recommended here:

http://www.chemaxon.com/forum/viewpost16681.html&highlight=neutralize+transform#16681 />
This was achieved as follows:
 standardize -c final-stand.xml 2008LiData.sdf -f sdf -o 2008LiData_stand.sdf 

I notice (upon viewing the molecules) that this does not appear to have taken care of N+ radicals, for example, that were present 
in my original SDF file.

Should this have happened, or have I simply misunderstood the function of Neutralize?

Is there anything obviously wrong with my script? I tried to remove all transformations which I thought were inconsistent with those carried out previously.

Following this, I tried to calculate the following sets of descriptors (N.B. the input file is the same 
as the output file above, save for the addition of a some more fields using a Python script).

cxcalc -S -o 2008LiData_stand_IC50_ID_act_CAdesc.sdf pka -t basic pka -t acidic logp mass wienerindex acceptorcount donorcount 2008LiData_stand_IC50_ID_act.sdf

>> CxcalcErrors.txt 2>&1

This failed to calculate pka, logp, acceptorcount or donorcount descriptors for entires 195 and 405.  

When I used an identical configuration script, save for the Neutralize statement, 
I was able to calculate all relevant desciptors without any exceptions being reported.

I'm using JChem 5.1.3, on a Windows XP machine (32 bit, Intel Pentium 4).

I attach all relevant files.

Thanks in advance for any assistance.

Quaternary amines are not neutralized by the "neutralize" action, and for example a tertiary amine with a radical is taken into account as a quaternary amine. I think this is the case in this situation.

http://www.chemaxon.com/forum/viewpost16681.html&highlight=neutralize+transform#16681 />
This was achieved as follows:
 standardize -c final-stand.xml 2008LiData.sdf -f sdf -o 2008LiData_stand.sdf 

Is there anything obviously wrong with my script? I tried to remove all transformations which I thought were inconsistent with those carried out previously.

Following this, I tried to calculate the following sets of descriptors (N.B. the input file is the same 
as the output file above, save for the addition of a some more fields using a Python script).

cxcalc -S -o 2008LiData_stand_IC50_ID_act_CAdesc.sdf pka -t basic pka -t acidic logp mass wienerindex acceptorcount donorcount 2008LiData_stand_IC50_ID_act.sdf

>> CxcalcErrors.txt 2>&1

This failed to calculate pka, logp, acceptorcount or donorcount descriptors for entires 195 and 405.  

When I used an identical configuration script, save for the Neutralize statement, 
I was able to calculate all relevant desciptors without any exceptions being reported.

I'm using JChem 5.1.3, on a Windows XP machine (32 bit, Intel Pentium 4).

I attach all relevant files.

Thanks in advance for any assistance.

The 195th and 405th molecules in the 2008LiData_stand_IC50_ID_act.sdf have valence error. Transforms can easily cause valence errors, please check your transformations in your standardizer configuration file.

I think the  file 2008LiData_stand_IC50_ID_act.sdf was created using a different standardier config than the attached final-stand.xml, becuse I don't get any errors if I standardize 2008LiData.sdf using final-stand.xml config, and then calculate the listed properties with cxcalc:

standardize -c final-stand.xml 2008LiData.sdf -f sdf | cxcalc pka -t basic pka -t acidic logp mass wienerindex acceptorcount donorcount >result.txt

I attached result.txt, which includes results for molecules 195 and 405.

Zsolt

Dear Zolt,

Thank you for taking the time to look at this and clarify the expected behaviour of Neutralize vis-a-vis N+ radicals.

I believe I may have made a typo at some point, which meant that the configuration file I handed you was not the same as the one I actually used originally. Having manually corrected some of the original SMILES strings (to remove N+ radicals), using the posted config script and cxacalc as specified didn't generate any exceptions.

Sorry for inadvertently wasting your time.

Regards,

Richard