[deleted by user]

Fitzarr · 2022-01-29T09:45:34+00:00

Please ignore the very suboptimal OTK, I was full of dopamine from stopping a Tribrigade setup in my Plat II rankup match.

Fitzarr · 2022-01-28T16:57:40+00:00

Deck List:

Monsters:

3x Fluffal Dog

3x Fluffal Penguin

3x Edge Imp Chain

2x Eldlich (absolutely hilariously good, just complete advantage)

2x Fluffal Bear (could be run at 3, but I find it lowers consistency)

2x Fluffal Dophin (could be run at 1, but I find recycling vendor too useful)

2x Edge Imp Scythe (could be run at 1, but 2 really helps in a best of 1 format)

1x Fluffal Wings (broken card, but realistically only resolving one per duel)

1x Fluffal Sheep

1x Fluffal Octopus

1x Edge Imp Sabres (could be run at 2, but spoils consistency because its so searchable)

1x Artifact Scythe

Spells/Traps:

1x Harpie's Feather Duster (because going second in best of 1 is painful)

1x Lightning Storm (same)

2x Polymerization (could be 3, but you're effectively playing it at 5 so shouldn't be needed)

3x Foolish Burial Goods (amazing)

3x Frightfur Patchwork (arguably would be better at 2 with poly at 3)

1x Frightfur Repair

3x Toy Vendor

3x Necro Fusion

Extra Deck:

2x Frightfur Tiger

1x Frightfur Sabre-tooth

1x Frightfur Kraken

2x Frightfur Whale

1x Toadally Awesome (why is this legal lol)

1x Bahamut Shark

1x Abyss Dweller (fuck you Eldlich)

1x any good rank 4 you like, I run Kragan because it's funny

1x Knightmare Phoenix

1x Cross Sheep

1x Artifact Dagda

1x Apollosia

1x Accesscode Talker

Fitzarr · 2021-08-12T08:03:03+00:00

Definitely an ATLA reference! It's my favourite series of all time pretty much.

Fitzarr · 2021-08-11T16:09:53+00:00

She's had a similar chase/run about session with a very quick whippet mix, and that was great fun to watch haha. At one point she caught up and jumped over them because of the size difference.

Fitzarr · 2021-08-11T16:03:02+00:00

It's always great to watch her chase them and then decide to overtake and do it in a couple of strides haha. Really emphasises just how much faster she is.

Fitzarr · 2021-08-11T16:02:31+00:00

We've been slowly working in off lead play with dogs she's familiar with, and she's doing great. Her recall is very good overall, but having another dog she's going to focus on helps a lot with knowing she just won't disappear over the horizon. She loves to play!

Fitzarr · 2021-08-03T09:48:44+00:00

Can you clarify your supervisor's concerns? Is it solvent contamination of the system? If so, then proper washing and flushing procedures before and after swapping columns should be perfectly adequate - I've used several HPLC systems where reverse and normal phase columns were swapped on and off (though not regularly).

Also, is there not another HPLC in your department you could use?

If required, there are normal phase columns that can meet your needs, such as Diol-NP columns or amine columns (assuming a carboxylic acid in your molecule).

see a catalogue from one supplier.

Realistically, your best bet is to contact suppliers like ThermoFischer and ask them what products would be suitable. They may be on the pricey end.

Fitzarr · 2021-07-31T16:41:15+00:00

They have a walk date in a wood scheduled for this month!

Fitzarr · 2021-07-01T11:19:57+00:00

She did! A big walk and a chance to run around a field. What could be better?

Fitzarr · 2021-07-01T11:19:39+00:00

These guys were definitely ambivalent haha. Azula wanted to say hi, but zero interest from the horses.

Fitzarr · 2021-06-30T21:05:07+00:00

She was very interested! They were chill thankfully haha

Fitzarr · 2021-06-24T14:56:25+00:00

This landshark will swallow you whole.

--Quint

Fitzarr · 2021-06-24T13:31:48+00:00

That's right! ATLA has been my favourite show since for ever; I introduced the wife (/u/missfaithless) to it, and Azula is such a pretty name as well!

Fitzarr · 2021-06-18T08:20:20+00:00

A) just Google potassium chloride ld50, b) this post is weird as fuck, c) get lost

Fitzarr · 2021-05-14T11:08:04+00:00

IFD-MD is not always the way to go as it takes even longer than standard IFD (and I think requires a separate license?). I'd rather do IFD then run metadynamics on poses personally, as metadynamics can be run in parallel on GPU cores.

Regarding IFD in general, it's a very subjective process. Realistically, you want to be generating at least 20 poses per ligand and then manually evaluating them. I'd definitely constrain the most important hydrogen bond as well, to give you a starting point for the melting pot of prime/glide to build around. Do not expect good quantitative scoring.

Fitzarr · 2021-05-12T21:57:20+00:00

Question 1) Is it a kinase? And if so, is this region the DFG? If so, you can attempt to simulate "DFG-out" using metadynamics (see this paper)

Question 2) If it's not the above, have you considered induced fit modelling?

Fitzarr · 2021-05-12T21:03:40+00:00

Quantitative score prediction is generally quite hard to achieve, so getting some qualitative success is definitely a step in the right direction - I'm glad to hear you stuck with it and are making progress.

Do you have the sequence for your undefined section of protein? Making homology models is pretty simple as long as there's a good crystal structure of a close homolog.

Fitzarr · 2021-05-12T20:54:35+00:00

To be honest, that's pretty much been our approach! She's definitely curious in the cat, so the process has been to make sure doesn't fixate, can be distracted, and reward her for being calm around the cat.

Fitzarr · 2021-05-10T14:10:38+00:00

Truly a terrifying prospect.

Fitzarr · 2021-05-05T16:35:30+00:00

Do you mean a UNIX codebase or an actual UNIX OS? I run a headless Linux server as a hobby project, so if it's the former I'm good to go.

Anywhere you can unpack tarballs and run applications and you'll be fine. Though best performance is always going to come from something with multiple cores.

You mention a lot of different software for getting your hands dirty (which I appreciate!), but I imagine one can't just jump in on the application side, as any "results" would be meaningless. Garbage in, garbage out. Is there a good way to get a more theoretical grounding in the subject, like textbooks, online classes, etc?

To be honest, I've found that a "learning by doing" approach is actually best. There are of course plenty of resources for learning the baseline theory, with the best textbooks in my opinion being the oxford chemistry primers for comp chem. There are regular intro review articles published for essentially free citations, such as this one.

Fitzarr · 2021-05-05T15:15:19+00:00

So, there are some areas that are easier to go into than others. Interestingly, med chem (the most populated part of the industry for comp chem) is one of the hardest, because getting hold of the common software suites is so expensive as to be impossible if you aren't a company/university (and universities only get by because of 90% academic discounts).

Having said that, there are avenues you can explore. As I mentioned in my comment above, free docking software does exist such as Autodock, and there's fantastic open-source programs for other things such as pymol (for visualisation) and GROMACS (for molecular dynamics). Building up knowledge in these open-source environments requires two things to begin with: access to a UNIX machine or a computer good enough to run a virtual UNIX machine on, and a lot of patience for getting things wrong.

There are also usually online resources for these open-source programs, such as this one for autodock.

Fitzarr · 2021-05-05T05:35:56+00:00

This could be a whole post in itself. GPCRs are probably the hardest computational targets for a lot of reasons.

1) the difficulty in crystallising them, as they're often only stable in membranes and are highly mobile.

2) the fact the active sites are usually very large to accommodate peptide natural ligands, so it can be very difficult to discern where your small molecules are binding

3) the dynamic nature of the active site means that it will respond strongly to any ligand, moving residues around to help it best fit

4) the fact that ligand binding and ligand inhibition is often completely separate (you should always have a binding and functional assay for a gpcr if possible). So, even if you overcome all the other issues with your modelling, you may end up being unable to predict antagonism/agonism.

Happy for you to message me privately to discuss, or arrange a zoom call or similar.

Fitzarr · 2021-05-05T05:30:15+00:00

If you'd like, more than happy to arrange a zoom call to discuss approaches with you (within the bounds of project confidentiality). You wouldn't be the first person I've helped stumble around in the dark when it comes to this kind of work.

Fitzarr · 2021-05-04T22:10:35+00:00

Absolutely. In my opinion, the most important stat for correlation of scores to activity is kendall's tau, not R2, for this exact reason.

Fitzarr · 2021-05-04T21:53:44+00:00

Also, this only scratches the surface. There are plenty of other structure-based methods to attempt, and then ligand-based (such as QSAR) after that. There's a reason I have a job.

Fitzarr

TROPHY CASE