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opensourceantibiotics / murligase

Everything to do with the Mur Ligase Project
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Competition Submission - Vandan Revanur #73

Open vandan-revanur opened 2 years ago

vandan-revanur commented 2 years ago

ligands_at_site_349.csv ligands_at_site_373.csv ligands_at_site_374.csv ligands_at_site_378.csv

Submitter: Vandan Revanur

Files Submitted: 4 CSV files, each containing a list of ligands that can attach to the protein at the different allosteric sites respectively. The ligands are generated using a CNN based tool called: DeepFrag ( https://git.durrantlab.pitt.edu/jdurrant/deepfrag/ ). They are ranked based on the docking score.

@mattodd As per #69, I tried to upload the files directly to the murligase/FIle Diary/2022 folder by pushing directly to master, which does not seem to work. I also tried creating a PR and that also does not work. In both cases I get an error:

remote: Permission to opensourceantibiotics/murligase.git denied to vandan-revanur

So I attach the files here directly.

edwintse commented 2 years ago

Hi @vandan-revanur, thanks for your submission! We just had a few questions regarding the compounds:

Screenshot 2022-05-16 at 10 41 11 am
vandan-revanur commented 2 years ago

Hello @edwintse ,

Sorry for the delayed response.

For the cases of repetition, please take the representative compound from each set of repetition. And regarding the smiles that contain different compounds, is it possible to have consider both of them separately as potential candidates? (I am not well versed in the chemical compounds themselves since my background is not from Chemistry)

mattodd commented 2 years ago

OK, @edwintse could you summarise in one sheet the structures of representative members here? Are the molecular weights at least 3 heavy atoms more than the original frags?

I'm confused by the counterion, or accompanying molecule, in each case. What's that doing? @vandan-revanur do you have a picture of what the molecules are doing in terms of their interaction with the protein?

edwintse commented 2 years ago

Here are the structures from the 4 sites

drc007 commented 2 years ago

Am I interpreting the structures correctly? Aren't these aminals and thus unstable?

vandan-revanur commented 2 years ago

OK, @edwintse could you summarise in one sheet the structures of representative members here? Are the molecular weights at least 3 heavy atoms more than the original frags?

I'm confused by the counterion, or accompanying molecule, in each case. What's that doing? @vandan-revanur do you have a picture of what the molecules are doing in terms of their interaction with the protein?

I really am not aware of what is happening with the accompanying molecule that you mentioned.

mattodd commented 2 years ago

Agree 100% with @drc007 that the aminals will not play nice in water/protein, and would be hard to make. The counter-ion also makes me uneasy. @vandan-revanur did you have any other suggestions you'd like to make that don't have these chemistry issues?

vandan-revanur commented 2 years ago

@mattodd I am afraid I do not have any suggestions to alleviate the chemistry issues. Can we go ahead with the compound for site 349, since it looks reasonable to synthesise, as @edwintse opined?

vandan-revanur commented 2 years ago

Here are the structures from the 4 sites

  • Only the compound for site 349 looks reasonable to synthesise
  • The rest of the compounds for the remaining sites are not commercially available and would also be very difficult to synthesise Mur Ligase Entry 2 Vandan Revanur

@mattodd @edwintse Could you please go ahead with the synthesis of compound at the 349 site since it looks reasonable to synthesize?

edwintse commented 2 years ago

Hi @vandan-revanur, yes we will go ahead and make that compound. I've just ordered the starting material for the synthesis.