In order to keep folks up-to-date with X-ray structure releases I’ll post in here whenever we update Fragalysis.
Any issues just let me know.
This is an excellent idea!
Some new structures are now live on Fragalysis and there are a few things to note:
- We are now using a different crystal form (same crystal form as immature structures (Mpro-N###) but with mature protein)
- This crystal form has more open crystal packing and more flexibility in loops around S3/S4 region (good for ligands targeting S4)
- The two dimer subunits are not identical and the ligand is not always bound in both
- On Fragalysis the new structures will be labelled as P####_#A/B_LigandID (where P#### refers to the dataset and #A/B refers to the protein chain and the ligand e.g. 0A is the first ligand in chain A)
| Dataset | CID | Site | Fragalysis Link | |
|---|---|---|---|---|
| Mpro-P0157 |
PET-UNK-29afea89-2 |
Isoquinoline |
https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/PET-UNK-29afea89-2/L/P/C |
|
| Mpro-P0187 | MAT-POS-de59a476-4 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-de59a476-4/L/P/C | |
| Mpro-P0208 | EDG-MED-971238d3-4 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDG-MED-971238d3-4/L/P/C | |
| Mpro-P0033 | MIC-UNK-91acba05-6 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MIC-UNK-91acba05-6/L/P/C | |
| Mpro-P0047 | LON-WEI-adc59df6-47 | Ugi | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/LON-WEI-adc59df6-47/L/P/C |
Thanks, Daren, and I certainly need to revise how I’m thinking about structural elaboration from the methyl group of PET-UNK-29afea89-2. This binding mode does bring the methyl tantalizingly close to the catalytic cysteine although I (currently) believe that it will be difficult to present a covalent warhead to it.
Apologies for the delays between updates - a challenging run at Diamond and a few technical issues/corner cases were flushed out when uploading data from the new crystal form onto Fragalysis.
There are still some gremlins lurking including proper generation of the reference cartoon and when we fix these it is likely that previous snapshots will no longer work (sorry), but hopefully the data is still useful for design purposes.
If you spot any other issues, please let us know.
| Dataset | Compound Code | Structure | Site | Fragalysis |
|---|---|---|---|---|
| Mpro-P0008 | ERI-UCB-ce40166b-17 |
|
Quinolone | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ERI-UCB-ce40166b-17/L/P/C |
| Mpro-P0009 | MAT-POS-f2460aef-1 | Ugi | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-f2460aef-1/L/P/C | |
| Mpro-P0010 | PET-UNK-c9c1e0d8-4 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/PET-UNK-c9c1e0d8-4/L/P/C | |
| Mpro-P0012 | ALP-POS-ce760d3f-2 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ALP-POS-ce760d3f-2/L/P/C | |
| Mpro-P0016 | ALP-POS-64a710fa-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ALP-POS-64a710fa-1/L/P/C | |
| Mpro-P0017 | ALP-POS-ce760d3f-8 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ALP-POS-ce760d3f-8/L/P/C | |
| Mpro-P0018 | ERI-UCB-d6de1f3c-2 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ERI-UCB-d6de1f3c-2/L/P/C | |
| Mpro-P0019 | PET-UNK-c9c1e0d8-3 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/PET-UNK-c9c1e0d8-3/L/P/C | |
| Mpro-P0022 | VLA-UCB-29506327-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/VLA-UCB-29506327-1/L/P/C | |
| Mpro-P0026 | ALP-POS-8b8a49e1-4 | Moonshot - active site | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ALP-POS-8b8a49e1-4/L/P/C | |
| Mpro-P0030 | EDG-MED-0e5afe9d-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDG-MED-0e5afe9d-1/L/P/C | |
| Mpro-P0031 | BEN-DND-c852c98b-10 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/BEN-DND-c852c98b-10/L/P/C | |
| Mpro-P0034 | EDJ-MED-92e193ae-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDJ-MED-92e193ae-1/L/P/C | |
| Mpro-P0038 | EDG-MED-0e5afe9d-3 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDG-MED-0e5afe9d-3/L/P/C | |
| Mpro-P0039 | EDG-MED-971238d3-5 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDG-MED-971238d3-5/L/P/C | |
| Mpro-P0041 | MAT-POS-090737b9-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-090737b9-1/L/P/C | |
| Mpro-P0045 | TRY-UNI-2eddb1ff-7 | Aminopyridine | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/TRY-UNI-2eddb1ff-7/L/P/C | |
| Mpro-P0053 | BRU-THA-92256091-17 | Ugi | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/BRU-THA-92256091-17/L/P/C | |
| Mpro-P0056 | RAL-THA-4aa06b95-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-4aa06b95-1/L/P/C | |
| Mpro-P0057 | MAT-POS-6c284e65-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-6c284e65-1/L/P/C | |
| Mpro-P0060 | MIC-UNK-45817b9b-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MIC-UNK-45817b9b-1/L/P/C | |
| Mpro-P0061 | RAL-THA-2d450e86-26 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-2d450e86-26/L/P/C | |
| Mpro-P0063 | RAL-THA-2d450e86-33 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-2d450e86-33/L/P/C | |
| Mpro-P0064 | RAL-THA-2d450e86-10 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-2d450e86-10/L/P/C | |
| Mpro-P0065 | RAL-THA-2d450e86-13 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-2d450e86-13/L/P/C | |
| Mpro-P0066 | RAL-THA-2d450e86-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-2d450e86-1/L/P/C | |
| Mpro-P0068 | RAL-THA-2d450e86-17 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-2d450e86-17/L/P/C | |
| Mpro-P0069 | RAL-THA-2d450e86-7 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-2d450e86-7/L/P/C | |
| Mpro-P0075 | RAL-THA-2d450e86-16 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-2d450e86-16/L/P/C | |
| Mpro-P0108 | RAL-THA-2d450e86-6 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-2d450e86-6/L/P/C | |
| Mpro-P0111 | ALP-UNI-3735e77e-2 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ALP-UNI-3735e77e-2/L/P/C | |
| Mpro-P0114 | ALP-POS-869ac754-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ALP-POS-869ac754-1/L/P/C | |
| Mpro-P0121 | MAT-POS-fce787c2-3 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-fce787c2-3/L/P/C | |
| Mpro-P0124 | BEN-DND-c852c98b-5 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/BEN-DND-c852c98b-5/L/P/C | |
| Mpro-P0125 | EDG-MED-971238d3-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDG-MED-971238d3-1/L/P/C | |
| Mpro-P0129 | MAT-POS-fce787c2-5 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-fce787c2-5/L/P/C | |
| Mpro-P0130 | RAL-THA-05e671eb-10 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-05e671eb-10/L/P/C | |
| Mpro-P0141 | MAT-POS-f9802937-7 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-f9802937-7/L/P/C | |
| Mpro-P0148 | EDG-MED-5d232de5-3 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDG-MED-5d232de5-3/L/P/C | |
| Mpro-P0160 | EDG-MED-5d232de5-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDG-MED-5d232de5-1/L/P/C | |
| Mpro-P0171 | EDG-MED-5d232de5-6 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDG-MED-5d232de5-6/L/P/C | |
| Mpro-P0179 | VLA-UCB-50c39ae8-7 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/VLA-UCB-50c39ae8-7/L/P/C | |
| Mpro-P0186 | ALP-POS-c3a96089-4 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ALP-POS-c3a96089-4/L/P/C | |
| Mpro-P0213 | MAT-POS-e69ad64a-2 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-e69ad64a-2/L/P/C | |
| Mpro-P0224 | EDJ-MED-8c98ee63-2 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDJ-MED-8c98ee63-2/L/P/C | |
| Mpro-P0240 | BEN-DND-f2e727cd-5 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/BEN-DND-f2e727cd-5/L/P/C | |
| Mpro-P0243 | EDJ-MED-d08626de-3 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDJ-MED-d08626de-3/L/P/C | |
| Mpro-P0394 |
LON-WEI-9739a092-9 |
Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/PCM-0222105/L/P/C | |
| Mpro-P0578 | RAL-THA-4aa06b95-7 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/RAL-THA-4aa06b95-7/L/P/C | |
| Mpro-P0601 | EDJ-MED-e4b030d8-11 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDJ-MED-e4b030d8-11/L/P/C | |
| Mpro-P0602 | EDJ-MED-37aac4bd-4 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/EDJ-MED-37aac4bd-4/L/P/C | |
| Mpro-P0607 | MAT-POS-a13804f0-3 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-a13804f0-3/L/P/C | |
| Mpro-P0626 | ALP-POS-fe871b40-11 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ALP-POS-fe871b40-11/L/P/C | |
| Mpro-P0627 | MAT-POS-78e1d523-1 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-78e1d523-1/L/P/C | |
| Mpro-P0661 | MAT-POS-932d1078-3 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/ALP-POS-fe871b40-11/L/P/C | |
| Mpro-P0996 | MAT-POS-4223bc15-30 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-4223bc15-30/L/P/C | |
| Mpro-P1007 | MAT-POS-4223bc15-3 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-4223bc15-3/L/P/C | |
| Mpro-P1015 | MAT-POS-4223bc15-2 | Isoquinoline | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/MAT-POS-4223bc15-2/L/P/C |
2 Likes
There are a handful of new structures now live plus you can now inspect electron density and PanDDA event maps in Fragalysis by clicking the D button and selecting which maps you want to see (we are aware of some teething issues still but if you notice anything odd please do flag).
New structures now online:
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| Dataset | Compound ID | Structure | Fragalysis |
|---|---|---|---|
| Mpro-P2001 | JAN-GHE-5a013bed-2 | https://fragalysis.diamond.ac.uk/viewer/react/preview/direct/target/Mpro/mols/JAN-GHE-5a013bed-2/L/P/C |
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| Dataset | Compound ID | Structure |
|---|---|---|
| Mpro-P0143 | VLA-UCB-34f3ed0c-11 | |
| Mpro-P0950 | ALP-POS-e0fe77e5-13 | |
| Mpro-P2113 | MAT-POS-1bed62cf-3 | |
| Mpro-P2222 | EDJ-MED-8bb691af-4 |
1 Like
| Dataset | Compound Code | Structure |
|---|---|---|
| Mpro-P2724 | EDJ-MED-976a33d5-1 | |
| Mpro-P2730 | ALP-POS-ecbed2ba-12 | |
| Mpro-P3038 | MAT-POS-e48723dc-2 | |
| Mpro-P3050 | MAT-POS-50a80394-1 | |
| Mpro-P3054 | MAT-POS-50a80394-2 | |
| Mpro-P3074 | ALP-POS-133e7cd9-2 |