representation of pka microspecies

While submitting nitroimidazole to a pka & microspecies distribution calculation at pH=7 I found to my surprize that the nitro group, initially represented with separated charges, became O=N(=O) in the microspecies retrieved by





plugin.getMsMolecule(i).toFormat("smiles");





Is there a standardizing ghost haunting getMsMolecule? If so, how can I tell it which standardize.xml to use??

fbonachera wrote:

While submitting nitroimidazole to a pka & microspecies distribution calculation at pH=7 I found to my surprize that the nitro group, initially represented with separated charges, became O=N(=O) in the microspecies retrieved by plugin.getMsMolecule(i).toFormat("smiles"); Is there a standardizing ghost haunting getMsMolecule? If so, how can I tell it which standardize.xml to use??

Standardization is built-in for each plugin. Most plugins perform aromatization, nitro-group standardization:

Code:

[O-]-[N+] >> O=N

and sulphynil group standardization:

Code:

[#6][S+:1]([#6])[#8-:2]>>[#6][S:1]([#6])=[O:2]

The pKa and microspecies calculation also removes explicit hydrogens.


Since our calculations expect the input molecule to be in standardized form, it is not possible to perform the calculations on the original molecule. Unfortunately, as a side effect, the microspecies are also constructed from the standardized molecule therefore and not from the original one. As a workaround, you may apply a reverse-standardization to have the ionic forms. I attach the corresponding standardizer.xml. However, explicit H atoms cannot be safely added since we can only transform all implicit H-s to explicit.





Example:

Quote:

standardize -c standardizer.xml "CS(=O)C(c1ccccc1)N(=O)=O" C([O-])C(C1=CC=CC=C1)[N+]([O-])=O

Remark: in earlier JChem versions the syntax of

Code:

<Dearomatize/>

is

Code:

<Action Act="dearomatize"/>

Thanks; restandardization shoud do... however, your response rises another doubt:





(a) sometimes standardization reshuffles atom order in a molecule


(b) pmapper also performs internal standardization [is this still the case once you remove the explicit lines from the config xml?]





Could it then happen that the pharmacophore flags spit out by pmapper no longer match the initial atom numbering in the input molecule?

fbonachera wrote:

Thanks; restandardization shoud do... however, your response rises another doubt: (a) sometimes standardization reshuffles atom order in a molecule (b) pmapper also performs internal standardization [is this still the case once you remove the explicit lines from the config xml?] Could it then happen that the pharmacophore flags spit out by pmapper no longer match the initial atom numbering in the input molecule?

(a) Yes, it happens if the standardizer config contains transformations that change the atoms - in our sample pharma-frag.xml and pharma-calc.xml removes small fragments in their <Removal> section; but it refers only to multi-fragment molecules (salt). Another example is <Dehydrogenize> or <Hydrogenize>. Plugin standardization contains <Dehydrogenize>. However, if your molecule does not contain H atoms then the atom order is preserved, even in the microsepcies: the nitro- and sulphynil group transformations and the aromatization do not change the atom order.





(b) If you remove the <StandardizerConfiguration> section from the pmapper config XML then no standardization will be performed, however, it is advisable that you input molecules would be at least aromatized in order to get correct results. If you use microspecies returned by the plugin then they are standardized. If your original input molecule does not contain explicit H atoms then the atom order is preserved. If you have multi-fragment molecules (salts) then the whole thing is problematic, since plugins handle only one fragment at a time.





Currently the pmapper output is not correct in case when the inner standardization changes the atom order. I will correct this on the next major JChem release - the output will reflect the original atom order with empty strings set for atoms not existing in the standardized version.