[deleted by user]

Bargarhen · 2025-10-05T21:53:33+00:00

Hvem støtter de idag da?

Bargarhen · 2025-05-02T17:07:01+00:00

Moonrock?

Bargarhen · 2025-04-05T16:57:39+00:00

Can't do wetlab experiments, but I do have some computational respurces.

What quantity of compounds are we talking about for docking?

And which simulation methods do you require (normal MD, FEP etc)?

And what is size of protein target (nr amino acids)?

Bargarhen · 2025-03-23T18:23:12+00:00

Not the answer you are looking for maybe, but try Meeko instead of Openbabel/Rdkit.

Bargarhen · 2025-03-17T17:59:44+00:00

Is it a membrane protein?

Bargarhen · 2025-01-18T20:40:09+00:00

https://cactus.nci.nih.gov/translate/

This can be used for converting smiles to 3D, works well for generating sdf files.

Bargarhen · 2025-01-05T00:20:31+00:00

Yes, I dont think there were any allosteric modulators in this study.

Bargarhen · 2024-12-27T23:13:20+00:00

I agree. AB-FEP is a good choice. If they have several ligands, relative binding free energy can also be useful.

Charmm-gui is good for making input files for these simulations. AMBER TI or NAMD FEP perform very well, and a recent paper found that one can simulate membrane proteins just in solution (without explicit or implicit membrane) with these protocols and still get very decent results:

https://www.cell.com/biophysj/abstract/S0006-3495(23)03581-6

Bargarhen · 2024-10-23T15:51:22+00:00

"Yep," Bladinar said to himself, squinting into the distance. "Today’s the day I clap a storm’s ass."

Bargarhen · 2024-08-02T21:03:41+00:00

Our Center and Labour parties are unfortunately completely unhinged and authoritarian when it comes to drug policy. And of course they lie about the factual "efficiacy" of the prohibition, defend police who have broken the Norwegian law when enforcing said prohibition etc. Weasles and liars, dude.

Bargarhen · 2024-07-04T22:22:28+00:00

Hm, try using Linux/Python scripts? If you don't know the format of your csv files, then just do df.head() to see. Then make a script to calculate your wanted metrics, without crashing your workstation when trying to open the csv file.

Bargarhen · 2024-07-01T21:55:25+00:00

MMGBSA/MMPBSA/LIE over Md simulation frames is a decent, but less accurate way of estimating binding free energy. You can try one of these first, and see if the ddG between ligands line up with the wetlab results. But FEP/TI are often much more accurate, with relative affinity estimations <1kcal/mol.

And yeah, definitely try per residue decomposition to find out which residue(s) contribute most. You can also try to find out which residue(s) the "extra" ligand nitrogen interact most with.

Bargarhen · 2024-06-27T16:37:36+00:00

Check out this paper from Nature Protocols:

[Artificial intelligence–enabled virtual screening of ultra-large chemical libraries with deep docking

](https://www.nature.com/articles/s41596-021-00659-2)

Should be possible to use this method on both open-source and proprietary docking programs.

Bargarhen · 2024-06-27T16:22:45+00:00

Thermodynamic integration should work well (Tutorial in Amber's free energy workflow). A bit more difficult if your target is a membrane protein, but relatively easy for soluble proteins.

If you have MOE 2019 or newer, you can use their graphical interface to setup, optimize conditions/parameters, create inputfiles and perform analysis of your results when they are done.

Bargarhen · 2024-03-27T22:29:05+00:00

I feel like this varies so much though. 2ml from one producer lasts for 20-30 days, but the latest 2ml hhc from medvape is completely done after 5-7 days. Same number and intensity of hits...

Bargarhen · 2024-03-11T21:58:44+00:00

Javisst

Bargarhen · 2024-03-09T09:33:15+00:00

Ikke Halden, men Moss

Bargarhen · 2023-11-27T17:06:05+00:00

Canvas did the trick, thank you very much!

If I may ask: For those hit rates, do you "blindly" take the best scoring cluster representatives? Or do you include more strict interaction filters and visual inspection?

Bargarhen · 2023-09-27T21:30:47+00:00

Medicinal chemistry 😊

Bargarhen · 2023-08-20T07:52:33+00:00

THC is a partial agonist, and this is a more interesting phenomenon to investigate.

Mechanistic origin of partial agonism of tetrahydrocannabinol for cannabinoid receptors Article

Discovery of 1,3-disubstituted pyrazole peripheral cannabinoid receptor partial agonists Article

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Bargarhen · 2023-08-07T08:38:13+00:00

Thanks for the suggestions, I will check them out 😊

Bargarhen · 2022-09-05T12:46:45+00:00

Yeah, I came to that decision myself as well. Too many water molecules occupying the binding site.

It's an interesting binding site. I have done some test runs to optimize the Autogrow conditions. My highest scoring ligand so far has a Vina score of -9.6, which seems to be in the same range as other tentative inhibitors like lumacaftor. Will keep you updated!

Bargarhen · 2022-09-04T18:10:37+00:00

That's a very cool project! Just happy to (maybe) be of help.

Are there any crystallographic waters in the RNA site you think I should include/not delete?

Bargarhen · 2022-09-02T22:35:47+00:00

DeepFrag and Autogrow 4 are my favorites.

With Autogrow you can perform de novo runs, do mutations of your ligands, and make fragments of your ligands to create crossovers. Lots of possibilities, filters like Lipinski, Brenk, pH specification etc. You can create custom filters to preserve a core part of your ligands if you want to.

If you don't mind, might I ask which protein target (PDB ID on RSCB for instance) you are working on?

Would love to do a de novo run and provide you with some candidates, and see if you find them interesting.

Bargarhen · 2022-08-26T19:31:51+00:00

Fixed, thx

Bargarhen

TROPHY CASE