Open Source SARS Nsp13 Site 3 Monthly Meeting #14: 17:00-18:00 BST, Monday 13th Nov 2023

TomkUCL commented 8 months ago

Date: Monday 13th Nov 2023 Time: 5pm BST (other times) Place: https://ucl.zoom.us/j/97172937586 Previous meeting recordings: https://www.youtube.com/@MedChemCoreD-UCLSoP Previous Meeting Issue: https://github.com/StructuralGenomicsConsortium/CNP4-Nsp13-C-terminus-B/issues/41

Who can come?: Anyone. No need to say anything unless you'd like to. If you'd like to contribute to these meeting issues, please join Github.

Attending: Team can be seen at https://github.com/orgs/StructuralGenomicsConsortium/teams/cnp4-nsp13

Slide decks: Please https://github.com/orgs/StructuralGenomicsConsortium/teams/cnp4-nsp13 remember that if you share slides/info, drag and drop those into a comment on this page, below. Very easy and saves @mattodd having to pester you.

Key Things This Month (please add if you'd like to focus on something

1) Finalising targets from the "Fixed Core" project after generation of focussed Enamine-able libraries by @toluene44 2) Update from @TomkUCL and Geoff Wells re Nsp13 MD simulations 3) Brief update on status of Nsp13 campaigns/assays by @ahsgc or @toluene44 (if available for meeting).

Agenda and Actions Arising:

Synthetic Chemistry

[ ] @TomkUCL to update with one slide on current status of his chemistry.
[ ] @TomkUCL to ship samples of all UCL compounds to UNC for evaluation, requiring RA codes. Did this shipment take place over the summer?
[ ] @ahsgc to maintain contact with Piramal re building block completion and delivery to UCL <-- all complete?

Assays

ATP-periodate remains the best control we have. @alvaro-magalhaes has shipped the lit indole compounds first identified by @jamesday100 (now published) https://github.com/StructuralGenomicsConsortium/CNP8-Nsp13-Indoles

Are there any CACHE competition icompounds (designed vs the RNA-binding site) that can be used as a comparator, or as a source of potential control compounds? Or as a source of a machine-learning model that could be used to predict better binders in a second round?

[ ] @TomkUCL has used UCL's Creoptix wave to evaluate all local UCL compounds. Data arising? (No control protein was being used. Toronto has used WDR5, UCL could use carbonic anhydrase, etc. Alignment could help publishing the work!)

Structures

[ ] Joe Newman to update on compound soaking. The compounds sent by @ahsgc were soaked, but nothing was observed bound. Joe was going to try with ATP-periodate and the original fragments. Joe to update if available.

AOB

NMR: @TomkUCL to update on discussions with Chris Waudby (UCL) on design of 19F ligand-protein NMR assay with Joe’s fragments as controls. @mattodd will buy a 500-member 19F frag library.

@jamesday100 raised the question of whether we should go back and examine the other sites highlighted in the original fragment screen. @kipUNC mentioned that compounds were designed, purchased and evaluated vs ATP- and RNA-binding sites. @kipUNC to dig up the data.

Next Meeting

Date: Monday 11th December 2023 Time: 5pm GMT (other times) Place: https://ucl.zoom.us/j/97172937586

TomkUCL commented 7 months ago

Update presentation.pdf

TomkUCL commented 7 months ago

@tmw20653 DEL results from Peter with docking scores.

DEL Screen Hits.pdf

StructuralGenomicsConsortium / CNP4-Nsp13-C-terminus-B