jchem thinks this is a query - then PMapper crashes!

Hi - I'm struggling against the following smiles:

O=C1n2c(S\c1=C/c1ccc(cc1)N1CCOCC1)nc1ccccc21

which makes my pharmacophore typing scheme  to crash with the following God-offending message:

Pharmacophore Typing failure for mol # 1 chemaxon.nfunk.jep.ParseException: Error while evaluating expression:
(SEARCH0(ATOMINDEX)||SEARCH1(ATOMINDEX)||SEARCH2(ATOMINDEX,1))&&!SEARCH3(ATOMINDEX,1,2)&&!SEARCH4(ATOMINDEX,2,3)&&!CONTAINS(Cationic,ATOMINDEX)&&!SEARCH5(ATOMINDEX,1)&&!SEARCH6(ATOMINDEX,1)&&!(SEARCH7(ATOMINDEX)&&(PLUGIN(pka,ATOMINDEX)<4||PLUGIN(pka,ATOMINDEX)>7))&&!(SEARCH8(ATOMINDEX,1))&&!(SEARCH9(ATOMINDEX,1,3))
    Calculation result is not defined for query molecules.

Indeed, if I import the wild smiles into mviewer, it gets a nice (a) label on the C atom #6 (the one in the thiazolone ring). But... there's nothing queryish about that smiles (which, to start with, ain't a smarts!) Very bizzare stuff!

 

Cheers,

Dragos

By the way - got another example in the mean time: Cc1ccc2n\c(-nc(C)c2c1)=N/c1ncc2C(=O)CCCc2n1

dragos wrote:

Hi - I'm struggling against the following smiles: O=C1n2c(S\c1=C/c1ccc(cc1)N1CCOCC1)nc1ccccc21 which makes my pharmacophore typing scheme  to crash with the following God-offending message: Pharmacophore Typing failure for mol # 1 chemaxon.nfunk.jep.ParseException: Error while evaluating expression: (SEARCH0(ATOMINDEX)||SEARCH1(ATOMINDEX)||SEARCH2(ATOMINDEX,1))&&!SEARCH3(ATOMINDEX,1,2)&&!SEARCH4(ATOMINDEX,2,3)&&!CONTAINS(Cationic,ATOMINDEX)&&!SEARCH5(ATOMINDEX,1)&&!SEARCH6(ATOMINDEX,1)&&!(SEARCH7(ATOMINDEX)&&(PLUGIN(pka,ATOMINDEX)<4||PLUGIN(pka,ATOMINDEX)>7))&&!(SEARCH8(ATOMINDEX,1))&&!(SEARCH9(ATOMINDEX,1,3))     Calculation result is not defined for query molecules. Indeed, if I import the wild smiles into mviewer, it gets a nice (a) label on the C atom #6 (the one in the thiazolone ring). But... there's nothing queryish about that smiles (which, to start with, ain't a smarts!) Very bizzare stuff!

The (a) label on the C atom indicates it's aromatic. If there is an aromatic atom in the molecule without any aromatic bonds connected to it, then the structure is recognized as query, I think. Lot of calculator plugins (e.g. pKa, which is calculated in this case) cannot handle lonely aromatic atoms.

dragos wrote:

By the way - got another example in the mean time: Cc1ccc2n\c(-nc(C)c2c1)=N/c1ncc2C(=O)CCCc2n1

I get  "Inconsistent molecular structure." error message for this structure. It has valence error end aromaticity errors.

So these are query or incorrect structures, that's why the exceptions are throw. In Marvin/JChem 5.4 we will introduce Structure Checker, which can help identifying this kind of errors, and can fix them, it they can be fixed automatically.

Zsolt

Dragos, please try running PMapper with "--ignore-error" command line options. It should ignore errors.

$ pmapper

PMapper 5.4.0alpha1, (C) 1999-2010 ChemAxon Ltd.
Determination of pharmacophore properties.

Usage:
  pmapper [options] [input files]

Options:
  -h, --help                    this help message
  -c, --config <filepath>       path of the XML configuration file
  -o, --output <filepath>       output file path (default: stdout)
  -t, --tag                     name of the SDFile tag to store the
                                Pharmacophore Map (default: PMAP)
  -S, --sdf-output              SDF output (otherwise only PMAP list)
  -g, --ignore-error                  continue with next molecule on error
  -v, --verbose                 print calculation warnings to the console

Examples:
  pmapper -c Pharmacophores.xml m.mol
  pmapper -S -t PHARMACOPHORES -c Pharmacophores.xml m.mol -o o.sdf

My colleagues will get back to you if it's not working. Sorry, we are quite busy because of the US UGM.

Zsolt

Thanks! I'm actually not calling pmapper as such, but the API plugin within my java codes. But don't worry - the message was just to let you know; we do not really need those weird compounds anyway (they are Zinc, and there are millions of others that behave properly).

 

Cheers!