Filter out covalent ligands

Hello,

First of all I really like the interactivity of the assay results/compound tracker. One thing that I’m missing is the distinction between covalent/non-covalent hits however. Would it be possible to filter on covalent compounds? Now you can add this as a property but I can not easily get a ranked list of the top non-covalent compounds in terms of pIC50?

Thanks!

I combined the exported data from the activity and compound tracker pages to generate a ranked list with the additional covalent columns. The spreadsheet is by default ranked by pIC50 within the subgroups of covalent/non-covalent… is this something like what you were looking for Bart?

I’ll let @mc-robinson come back on adding the covalent tag directly into the activity data export.

activity_data_with_covalent_filter.csv (68.2 KB)

Yes indeed, so being able to filter (in the top):
https://postera.ai/covid/submissions/compounds
on the Covalent_warhead column (like is now the case with assayed/ordered/made)

Thanks!

Which is the difference between “covalent_warhead” and “covalent_fragment” columns? How are they estimated/calculated? I am also interested in filtering covalent inhibitors, so I assume that covalent inhibitors are those with “True” in the covalent_warhead column.

Hi @santi.garcia-vallve, “covalent_warhead” indicates that the design itself contains a warhead. “covalent_fragment” is slightly outdated, but indicates that the design of a compound was inspired by a covalent fragment during the initial fragment expansion stage.

Just to hi-jack this a little bit, would it alos be possible to add in to the activity data export the fragalysis code for those compounds with structural data? @mc-robinson

1 Like

Thanks @Ben_DNDi, I’ll try to get that done and let you know when it’s available. For now, the list of all structures can be found in this file: https://github.com/postera-ai/COVID_moonshot_submissions/blob/master/structures/fragalysis_structures.csv

Hi @mc-robinson, sorry for asking again about this subject. How could I calculate if a compound (not from the COVID Moonshot) contains such a covalent_warhead? Is it possible to know it from the smiles? Which rules do you use to estimate this field? Any help is appreciate. I am interested in knowing if the initial compounds of a VS contains a covalent_warhead.
Thanks

Hi @santi.garcia-vallve, these were the warhead rules used, though please note that they are nowhere near exhaustive.

covalent_warhead_smarts = {
    'acrylamide' : '[C;H2:1]=[C;H1]C(N)=O',
    'acrylamide_adduct' : 'NC(C[C:1]S)=O',
    'chloroacetamide' : 'Cl[C;H2:1]C(N)=O',
    'chloroacetamide_adduct' : 'S[C:1]C(N)=O',
    'vinylsulfonamide' : 'NS(=O)([C;H1]=[C;H2:1])=O',
    'vinylsulfonamide_adduct' : 'NS(=O)(C[C:1]S)=O',
    'nitrile' : 'N#[C:1]-[*]',
    'nitrile_adduct' : 'C-S-[C:1](=N)',
    }