This post attempts to bring together the various parts of the work, including files. Eventually this issue will be merged with the relevant wiki page and closed. Files are available in the File Diary. Please briefly add anything missing.
May/June 2023
@mattodd and @TomkUCL shared sketches of cores that they were interested in preserving from a generative library @kipUNC had previously provided, designed vs. Nsp13 Site 3.
3 Aug 2023
@kipUNC and Travis Maxfield (UNC) shared enumerated files for two sets of compounds that were docked into Site 3 - the files contain the top scored compounds according to Glide. (which cores are these?)
@toluene44 noted that these still contained a high level of pyridine N-oxides, which was a motif we wanted to reduce in frequency. Travis then (Aug 8th 2023) re-selected a diverse set from each library to give these:
Sept?
@toluene44 enumerates 100K libraries for each core, using a diverse set of ca 3000 carboxylic acids at each position of the diamines. (Need description of how) These go to @kipUNC 31st Oct 2023 to start the virtual screening.
These files are [here]()
@qxsml synthesises Core 6 on a gram scale, starting from work reported by @AndyXGH.
Nov/Dec 2023.
@TomkUCL applies filters to the 100K libraries from @toluene44 to concentrate on the most attractive compounds and to make docking more manageable on smaller computers. Docking is done with PyRx/ AutoDock Vina. Workflow:
This post attempts to bring together the various parts of the work, including files. Eventually this issue will be merged with the relevant wiki page and closed. Files are available in the File Diary. Please briefly add anything missing.
May/June 2023 @mattodd and @TomkUCL shared sketches of cores that they were interested in preserving from a generative library @kipUNC had previously provided, designed vs. Nsp13 Site 3.
3 Aug 2023 @kipUNC and Travis Maxfield (UNC) shared enumerated files for two sets of compounds that were docked into Site 3 - the files contain the top scored compounds according to Glide. (which cores are these?)
nsp13-new-enumerated_decorated_cores-top-120.zip nsp13-new-generated_decorated_cores-top-100.zip
@toluene44 noted that these still contained a high level of pyridine N-oxides, which was a motif we wanted to reduce in frequency. Travis then (Aug 8th 2023) re-selected a diverse set from each library to give these:
nsp13-new-enumerated_decorated_cores_top_glide_diversity.csv
nsp13-new-generated_decorated_cores_top_glide_diversity.csv
Sept? @toluene44 enumerates 100K libraries for each core, using a diverse set of ca 3000 carboxylic acids at each position of the diamines. (Need description of how) These go to @kipUNC 31st Oct 2023 to start the virtual screening.
These files are [here]()
@qxsml synthesises Core 6 on a gram scale, starting from work reported by @AndyXGH.
Nov/Dec 2023. @TomkUCL applies filters to the 100K libraries from @toluene44 to concentrate on the most attractive compounds and to make docking more manageable on smaller computers. Docking is done with PyRx/ AutoDock Vina. Workflow:
This workflow applied to Core 6 Some of the most promising compounds from Core 6 in this analysis
Details are described in #43 and here.
These suggestions (best- and worst-performing) needed to be correlated with suggestions from @kipUNC to find a consensus set for synthesis.
13 Dec 2023 @kipUNC provides poses for the top 500 poses of one of the cores:
glide-nsp13-x0420-core1_top-500-scores.csv
(see File Diary for the sdf and pdb files)
The files seem to contain some errors or corruption, and need re-checking. Also the same analysis is required for the other cores.