HeuckLab

Official Heuck Lab account. Opinions are only mine.

[HeuckLab @HeuckLab]

Small thread on #membranecomplexity #lipiddomain #lipidraft
1/3 Considering the intricate and diverse composition of biological membranes, any attempt to define lipid rafts merely adds confusion when compared with the simpler definition of lipid domains.

[HeuckLab @HeuckLab]

@CitiusMag So stupid

[owl @owl_posting]

What could Alphafold 4 look like? (Sergey Ovchinnikov, Ep #3)

2 hours listening time

(links below)

To those in the (machine-learning for protein design) space, Dr. Sergey Ovchinnikov (@sokrypton) is a very, very well-recognized name.

A recent MIT professor (circa early 2024), he has played a part in a staggering number of recent great papers in the field: ColabFold, RFDiffusion, Bindcraft, automated design of soluble proxies of membrane proteins, elucidating what protein language models are learning, conformational sampling via Alphafold2, and many more. Of course, all these papers were group efforts, but Sergey's name comes up astonishingly frequently!

And even beyond the research that have come from his lab in the last few years, the co-evolution work he did during his PhD/fellowship also laid some of the groundwork for the original Alphafold paper, being cited twice in it.

This is a two hour conversation with him, asking every question I could think of. We talk about his own journey into biology research, an issue he has with Alphafold3, what Alphafold4-and-beyond models may look like, what research he’d want to spend a hundred million dollars on, and lots more.

Topics/institutions we discuss: @arcinstitute's Evo models, @HWaymentSteele's work, @IsomorphicLabs's AF2/AF3, and @EvoscaleAI's ESM models

Also, extremely grateful to Asimov Press (@asimovpress) for helping fund the travel + studio time required for this episode! They are a non-profit publisher dedicated to thoughtful writing on biology and metascience, such as articles over synthetic blood and interviews with plant geneticists. I myself have published within them twice! I highly recommend checking out their essays at https://t.co/67GCqrINa0, or reaching out to [email protected] if you’re interested in contributing.

Timestamps:
[00:00:00] Highlight clips
[00:01:10] Introduction + Sergey's background and how he got into the field
[00:18:14] Is conservation all you need?
[00:23:26] Ambiguous vs non-ambiguous regions in proteins
[00:24:59] What will AlphaFold 4/5/6 look like?
[00:36:19] Diffusion vs. inversion for protein design
[00:44:52] A problem with Alphafold3
[00:53:41] MSA vs. single sequence models
[01:06:52] How Sergey picks research problems
[01:21:06] What are DNA models like Evo learning?
[01:29:11] The problem with train/test splits in biology
[01:49:07] What Sergey would do with $100 million

[HeuckLab @HeuckLab]

Read the full letter from universities opposing 'government intrusion' https://t.co/omQSPUPlaa

[HeuckLab @HeuckLab]

Borg attack https://t.co/qbDOMebiOx
#T3SS

[HeuckLab @HeuckLab]

#poreformingtoxin

[Kausik Chattopadhyay @KausikChatt]

Happy to share our latest work from the lab published in Biochemistry @ACSPublications, @DBS_IISERM
@IiserMohali. Mechanistic Cooperation of the Two Pore-Forming Transmembrane Motifs Regulates the β-Barrel Pore Formation by Listeriolysin O | Biochemistry https://t.co/pmM4cGVyhu

[HeuckLab @HeuckLab]

#poreformingtoxin

[Francisco J. Enguita @fenguita]

CryoEM structure of the Clostridium perfringens epsilon pore-forming toxin (PDB code: 6RB9) #scivis #molecularart @dzine_ai @proteinimaging
https://t.co/R6G3xjL5kQ

[HeuckLab @HeuckLab]

#poreformingtoxin

[Kausik Chattopadhyay @KausikChatt]

Delighted to share this collaborative study with @SANTANU03277687 and his group in Journal of Material Chemistry B, studying pore-forming toxin action at aqueous-liquid crystal interface. https://t.co/qLPcJtDD1E

[Tiago Costa @CostaT_Lab]

With @jrpenades, we challenged AI co-scientist @GoogleAI to generate hypotheses. In just 2 days, it recapitulated our unpublished, experimentally confirmed mechanism for how cf-PICIs spread between bacterial species! 🤯 @imperialcollege @FlemingCentre

https://t.co/hXkZZco6vu

[Structure @Structure_CP]

Online now! High-resolution cryo-EM analysis visualizes hydrated type I and IV pilus structures from enterotoxigenic Escherichia coli https://t.co/P9tLV1HmEn

[HeuckLab @HeuckLab]

Structural basis for the pore-forming activity of a complement-like toxin | Science Advances https://t.co/QU8jodKBkW #poreformingtoxins

[HeuckLab @HeuckLab]

Actinoporin Fav bind to cholesterol clusters: Cryo-EM structures of a protein pore reveal a cluster of cholesterol molecules and diverse roles of membrane lipids https://t.co/W2jFCamO79 #poreformingtoxins

[HeuckLab @HeuckLab]

Cholesterol cluster as PFO binding site, back 2010. The cholesterol-dependent cytolysin family of gram-positive bacterial toxins https://t.co/z8NQB2MeZA #poreformingtoxin

[HeuckLab @HeuckLab]

#poreformingtoxin

[Tony Kulesa @kulesatony]

New review out today in Nature Biotech on nanopore-based protein sequencing.

Feels... like... something... coming... soon... 👀

[HeuckLab @HeuckLab]

@RubenPSanca Greater Lowell !

[HeuckLab @HeuckLab]

@OdedRechavi As stand it is just descriptive and incremental, and deal with it

[Gregor Anderluh @GAnderluh]

Protein-Membrane Interactions!

The course of @MOSBRIeu project focuses on studies of protein-membrane interactions by using model membranes and biophysical approaches.

Free of charge. More info and how to apply here: https://t.co/yInTzoCG0X

Deadline 31. 3. 2025.

[HeuckLab @HeuckLab]

Autoinhibition of dimeric NINJ1 prevents plasma membrane rupture https://t.co/HpxpDawbL0

[HeuckLab @HeuckLab]

A conceptual framework for understanding phase separation and addressi... https://t.co/xFgiiSfHiV

[HeuckLab @HeuckLab]

@MJGold Everyone vs Jacob!

[HeuckLab @HeuckLab]

Small-molecule GSDMD agonism in tumors stimulates antitumor immunity w... https://t.co/QtuSEWCQC8 #poreformingtoxins