mattodd
commented
12 months ago Joe Newman says "I have had a look at the latest soaks with the compounds Anwar sent, unfortunately I don’t see anything bound and the diffraction was generally ok. I am waiting on the ATP periodate and the original fragments to be shipped. I will try more soaks then and include those controls."
Date: Monday 10th July 2023 Time: 5pm BST (other times) Place: https://ucl.zoom.us/j/97172937586 Previous meeting recordings: https://www.youtube.com/@MedChemCoreD-UCLSoP (Sorry no recording for this meeting) Previous Meeting Issue: https://github.com/StructuralGenomicsConsortium/CNP4-Nsp13-C-terminus-B/issues/39
Who can come?: Anyone. No need to say anything unless you'd like to. If you'd like to contribute, please join Github.
Attending: @mattodd @tmw20653 @ahsgc, @toluene44, @kipUNC, @jamesday100 (Astex). 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.
Agenda and Actions Arising:
Synthetic Chemistry
[ ] @TomkUCL to update with one slide on current status of his chemistry, and that of Andy and @KangpingL . These molecules need to be tested locally and:
[ ] @TomkUCL to ship samples of all UCL compounds to UNC for evaluation, requiring RA codes.
[ ] @ahsgc to maintain contact with Piramal re building block completion and delivery to UCL.
Assays
ATP-periodate compound increasingly being used as control for assays. @TomkUCL has ordered some for UCL. Ken Pearce is setting up the unwindase assay as an extra option.
In the broader Nsp13 project (which are site-agnostic) there is an improved concordance between SPR and ATPase assay data, which may help to give greater confidence in the SPR data. (@SumeraMalik123 is currently examining 50 compounds in triplicate by ATPase assay to drill down into this) Separately, the first round of the CACHE competition is concluding and there is a substantial data set (of compounds designed vs the RNA-binding site) that we may be able to use 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.
Predictions/Modelling
Structures
AOB
Indole Compounds: @jamesday100 previously highlighted a conference poster on nsp13 inhibitors identified by group in Rome. Alvaro in the UCL lab is now making two representatives of this series and will report at a future meeting.
NMR: @TomkUCL to update on discussions with Chris Waudby (UCL) on design of 19F ligand-protein NMR assay with Joe’s fragments as controls.
@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 14th August 2023 Time: 5pm BST (other times) Place: https://ucl.zoom.us/j/97172937586