with MD, with AI MDemulators, with AF hacks, ...

Thanks for sharing. Not surprised but good to see data also for antibodies that squares really well with our analysis on protein design more generally
bsky.app/profile/maxf...

Exactly

Yea this is not the same of course, but it just popped up in my feed and was close enough in topic ;)
Still, there might be something there. Sample unbiased random flex and score with IF?

Inverse folding much more promising
bsky.app/profile/alic...

Personally skeptical of a paper making broad claims about such methods capturing mutation effects when their data is a single mutation in a single enzyme where effect is extensively studied & captured in many training data structures. AI
structure/dynamics prediction tools are very poor VAEs imo

Fantastic! Had 3 Qs after thread & think I understood from paper myself
1 were the 500 ligands v similar? - No, quite diverse
2 did they do "fair" real-life docking when comparing - i think so
3 is one limitation that all results are for one receptor & might not generalize? - probably
Would u agree?

Nice first step indeed. But were the ribosomal proteins ever the bottleneck? I'd expect rRNA and tRNAs first and can't rebuild without all the RNA modification enzymes. But probably IVTT anyway usually stops due to ATP depletion, right?

Precisely. And that's what we want to encourage: implement custom scoring suitable for your goal to try to mitigate the shortcoming of refolding metrics. Or, for novices who may not be able to do much in this regard, at least be skeptical of these metrics

Well many sequences require chaperones or only get structured in complex with something, but this is not so easy to compile data. Synthetic nonsense would probably be easiest but whether this can be well implemented in training without compromising positive performance is a question.

Ohh nice, hadn't seen that then! Might have reconsidered terminology in the title if I had.. 😅

I'd say so - AF2 just hasn't ever seen any negative data. We discuss this a bit in the paper although refrain from speculating to widely.

20/19
Or, you know, if bioRxiv is down / extremely slow again, download the pdf here:
www.fuerstlab.com/uploads/2025...

MSA struc as temp to ss I'd expect similar to MSA but maybe worth a shot. Energy based I guess will not fold nonsense, thus hard to implement in our tests except maybe in very low mutation regime; could test that in pMPNN background. Will think, thanks!

Thanks to Seva and Kerlen for their tireless effort to get the data as watertight as possible.
Here is the preprint link again:
www.biorxiv.org/content/10.6...
19/19