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Everything to do with the Mur Ligase Project
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Competition Submission - Finlay MacLean (WIP) #74

Open finlayiainmaclean opened 2 years ago

finlayiainmaclean commented 2 years ago

Please see attached ligands that are predicted to bind to the same allosteric pocket as the 373 fragment.

Our method can be largely broken down into two steps. A more complete description can be found in the attached document.

  1. Screening drug-like commercially available molecules and ranking by a custom scoring function (maximising docking score, druglikeliness, and minimising synthetic accessibility, globularity, and flexibility). We further filter the top hits by inclusion of a primary amine, druggability and medicinal chemistry filters, and ensure the ligand-protein interactions are similar to the 373 fragment and potent 754 inhibitor.

  2. Using the top ranked molecules as seeds, we'll use a molecular VAE to probe the latent space around the ligands to find adjacent ligands that further optimize the scoring function.

I have completed steps 1/2 and am depositing the top triaged hits here. It is not a generative method on its own. I will update this issue with part 2 when complete.

Summary and top hits

Part 1: image Part 2:

image
edwintse commented 2 years ago

Thanks @finlayiainmaclean for your entry! @mattodd here's the list of compounds and prices. Looks like they should all be purchasable for reasonable prices. Let me know what you think.

Mur Ligase Entry 3 Finlay MacLean

mattodd commented 2 years ago

All looks good to me. Order the ones that can be ordered now. If the others are in REAL then we should be able to order them - I know they don't yet exist! Maybe ask MCULE/Enamine for quote? @edwintse I'm guessing we want these to be sent directly to Warwick, right? Can you please reach out to @LauraDS1 to check (unless you'd like to respond here, Laura!)