Has Protein Folding Been Solved?

Recently Deepmind made big headlines with its AlphaFold success. Did it really "solve" protein folding? What did actually happen? In this video I explain what the protein folding problem is, why it's important, and what the current situation is.

The protein animation shown at 1 mins 13 seconds goes back to this publication:

Structure of the Cdc48 segregase in the act of unfolding an authentic substrate.
Cooney I, Han H, Stewart MG, Carson RH, Hansen DT, Iwasa JH, Price JC, Hill CP, Shen PS.
Science, 365(6452): 502-505 (2019).

Reused with permission.

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#science #education #biochemistry

0:00 Intro
0:35 What's the problem?
1:49 Why does it matter?
5:07 How to try and solve it
6:27 The CASP Competition
8:10 Alphafold 2
9:07 What does this mean?
10:42 Sponsor Message

[TIOS]

Refreshing to hear someone use “exponentially” when it actually applies.

[SangsungMeansToCome]

The silver rule of broadcasting: Whenever there is a question in a headline, the answer is always NO.

[jrherita]

Sabine - really appreciate you taking the time to explain these complex topics to us. Thank you!

[zeawoas]

A few clarifications:
CryoEM doesn't generally give better resolution (it was actually worse than crystallography until recently), but it also works on many proteins that are not amenable to crystallization (e.g. membrane proteins). That's why it's so useful.
Also, oligomers are not several amino acids interacting, but several distinct amino acid chains (i.e. proteins).

[epemsley]

My headphone cord thinks it's a protein...very annoying.

[mg]

As a biochemist who worked both with x-ray crystallography and cryo-EM, a few comments: a) this is an excellent video, but i also never expected anything other than awesome from Sabine b) even if alpha fold performs less well for complexes or unusual folds, still it would be great if it could releive the burden of having to determine the structures of hundreds upon hundreds of similar proteins. This would free up valuable people and equipment to concentrate on the very unusual and complicated structures c) even if it doesn't revolutionize basic biochemistry, it can be of tremendous help to pharmaceutical research as they often work on relatively common folds (e.g. spike protein of Covid when you already know the spike structures of several other coronaviruses)

[illogicmath]

Sabine's social work in disseminating knowledge on such a wide range of scientific topics is invaluable.

[datapro]

Hi Sabine, I'm echoing what a lot of other folks have already stated. I really enjoy the diversity of topics that you present, and your well thought out presentation too. Thank you.

[MarianneExJohnson]

"That's almost as many vacua as there are in String Theory" -- priceless 🤣

[johnhoebel]

Excellent. I learned so much in 12 minutes about a subject I was totally ignorant of.

[subhrodeepsaha]

I just started my PhD in peptide folding and chemistry and then comes this news!! 😅

[SWatchik]

Great explanation and nice seeing more Biology content on here, as a Biologist myself!

[davidhand]

The problem with AI is that even when it understands something, it can't teach us anything about what it's learned.

[RichMitch]

Congratulations on 200k, much deserved

[davidschroeder]

This was just an absolutely fascinating topic. I had heard of this problem years ago, but never bothered looking into it. Sabine's ability to unravel the complexity of such issues is remarkable.

[mattisalmela]

Protein structures can also be studied using NMR. This has the advantage of not having to crystallize proteins and having them in their "native" form in solution.

Great video as usual!

[asafnisan]

You deserve a lot of respect for exposing us to different domains and questions in science. In a very understandable way too.

[arik]

''some of you may have folded proteins yourself''
YES I HAVE

WeLL
IM ALIVE, that's why!~😂🤣

[paolo]

"That's as many as there are vacua in string theory" do we live in a world where string theory is more widely understood than protein folding?

[BryanWLepore]

CASP updated the scoring algorithm in 2014 and the top scores have increased linearly since then.

The C-alpha “IDDT” distance scoring is based only on C-alpha positions - that is one atom out of all other amino acid atomic positions. There are other scoring calculations too.