Sergey Ovchinnikov
@sokrypton.org
Scientist, Assistant Professor at MIT biology, #FirstGen
Reposted by Sergey Ovchinnikov
New preprint🚨
Imagine (re)designing a protein via inverse folding. AF2 predicts the designed sequence to a structure with pLDDT 94 & you get 1.8 Å RMSD to the input. Perfect design?
What if I told u that the structure has 4 solvent-exposed Trp and 3 Pro where a Gly should be?
Why to be wary🧵👇
Imagine (re)designing a protein via inverse folding. AF2 predicts the designed sequence to a structure with pLDDT 94 & you get 1.8 Å RMSD to the input. Perfect design?
What if I told u that the structure has 4 solvent-exposed Trp and 3 Pro where a Gly should be?
Why to be wary🧵👇
December 16, 2025 at 3:15 PM
New preprint🚨
Imagine (re)designing a protein via inverse folding. AF2 predicts the designed sequence to a structure with pLDDT 94 & you get 1.8 Å RMSD to the input. Perfect design?
What if I told u that the structure has 4 solvent-exposed Trp and 3 Pro where a Gly should be?
Why to be wary🧵👇
Imagine (re)designing a protein via inverse folding. AF2 predicts the designed sequence to a structure with pLDDT 94 & you get 1.8 Å RMSD to the input. Perfect design?
What if I told u that the structure has 4 solvent-exposed Trp and 3 Pro where a Gly should be?
Why to be wary🧵👇
Reposted by Sergey Ovchinnikov
As a bonus, here's a video of ProteinEBM folding up the fast-folder NTL9, rendered in stunning 2D by py2Dmol from @sokrypton.org! We hope models like ProteinEBM can serve as a step toward solving the "real" protein folding problem.
December 12, 2025 at 4:09 AM
As a bonus, here's a video of ProteinEBM folding up the fast-folder NTL9, rendered in stunning 2D by py2Dmol from @sokrypton.org! We hope models like ProteinEBM can serve as a step toward solving the "real" protein folding problem.
Reposted by Sergey Ovchinnikov
An energy-based model of protein conformational space can be used to predict structure from sequence, sample from the conformational landscape, rank structures, and predict mutation effects.
@sokrypton.org
www.biorxiv.org/content/10.6...
@sokrypton.org
www.biorxiv.org/content/10.6...
December 10, 2025 at 11:17 PM
An energy-based model of protein conformational space can be used to predict structure from sequence, sample from the conformational landscape, rank structures, and predict mutation effects.
@sokrypton.org
www.biorxiv.org/content/10.6...
@sokrypton.org
www.biorxiv.org/content/10.6...
Reposted by Sergey Ovchinnikov
I'm super excited to announce the first preprint of my PhD, together with Chenxi Ou and @sokrypton.org!
ML has revolutionized protein modeling, but crucial challenges remain. For example, we can't reliably predict complicated protein structures without MSAs, which limits what we can design.
ML has revolutionized protein modeling, but crucial challenges remain. For example, we can't reliably predict complicated protein structures without MSAs, which limits what we can design.
December 10, 2025 at 3:03 PM
I'm super excited to announce the first preprint of my PhD, together with Chenxi Ou and @sokrypton.org!
ML has revolutionized protein modeling, but crucial challenges remain. For example, we can't reliably predict complicated protein structures without MSAs, which limits what we can design.
ML has revolutionized protein modeling, but crucial challenges remain. For example, we can't reliably predict complicated protein structures without MSAs, which limits what we can design.
Reposted by Sergey Ovchinnikov
An interesting study from @aidenkzj.bsky.social, @abulnaga.bsky.social and @sokrypton.org that builds on our Progres model to find pairs of proteins with circular permutations:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
CIRPIN: Learning Circular Permutation-Invariant Representations to Uncover Putative Protein Homologs
Protein structure-based homology detection has been revolutionized by deep learning methods that can rapidly search massive databases. However, current structural search tools often miss proteins rela...
www.biorxiv.org
November 25, 2025 at 2:43 PM
An interesting study from @aidenkzj.bsky.social, @abulnaga.bsky.social and @sokrypton.org that builds on our Progres model to find pairs of proteins with circular permutations:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Sergey Ovchinnikov
Thrilled to share that the final piece of my PhD work is now on bioRxiv! biorxiv.org/content/10.1... With support from @nvidia and the @NSF, we used AlphaFold to screen 1.6M+ protein pairs, revealing thousands of potential novel PPIs. All data can be viewed at predictomes.org/hp
Proteome-wide in silico screening for human protein-protein interactions
Protein-protein interactions (PPIs) drive virtually all biological processes, yet most PPIs have not been identified and even more remain structurally unresolved. We developed a two-step computational...
biorxiv.org
November 12, 2025 at 9:26 PM
Thrilled to share that the final piece of my PhD work is now on bioRxiv! biorxiv.org/content/10.1... With support from @nvidia and the @NSF, we used AlphaFold to screen 1.6M+ protein pairs, revealing thousands of potential novel PPIs. All data can be viewed at predictomes.org/hp
A few py2Dmol updates 🧬
py2dmol.solab.org
Integration with AlphaFoldDB (will auto fetch results). Drag and drop results from AF3-server or ColabFold for interactive experience! (1/4)
py2dmol.solab.org
Integration with AlphaFoldDB (will auto fetch results). Drag and drop results from AF3-server or ColabFold for interactive experience! (1/4)
November 19, 2025 at 8:15 AM
A few py2Dmol updates 🧬
py2dmol.solab.org
Integration with AlphaFoldDB (will auto fetch results). Drag and drop results from AF3-server or ColabFold for interactive experience! (1/4)
py2dmol.solab.org
Integration with AlphaFoldDB (will auto fetch results). Drag and drop results from AF3-server or ColabFold for interactive experience! (1/4)
Is 3D dragging you down? Wish you could instead use the 2D ColabFold representation for all your work? 🤓
Introducing: py2Dmol 🧬
(feedback, suggestions, requests are welcome)
Introducing: py2Dmol 🧬
(feedback, suggestions, requests are welcome)
October 29, 2025 at 1:39 AM
Is 3D dragging you down? Wish you could instead use the 2D ColabFold representation for all your work? 🤓
Introducing: py2Dmol 🧬
(feedback, suggestions, requests are welcome)
Introducing: py2Dmol 🧬
(feedback, suggestions, requests are welcome)
October 28, 2025 at 3:34 AM
Will it bind? A little worried about all the "TTTTTTT" 🧐 But looks cool 😎
October 27, 2025 at 12:07 AM
Will it bind? A little worried about all the "TTTTTTT" 🧐 But looks cool 😎
Reposted by Sergey Ovchinnikov
Thrilled to announce our new preprint, “Protein Hunter: Exploiting Structure Hallucination within Diffusion for Protein Design,” in collaboration with @Griffin, @GBhardwaj8 and @sokrypton.org
🧬Code and notebooks will be released by the end of this week.
🎧Golden- Kpop Demon Hunters
🧬Code and notebooks will be released by the end of this week.
🎧Golden- Kpop Demon Hunters
October 13, 2025 at 3:45 PM
Thrilled to announce our new preprint, “Protein Hunter: Exploiting Structure Hallucination within Diffusion for Protein Design,” in collaboration with @Griffin, @GBhardwaj8 and @sokrypton.org
🧬Code and notebooks will be released by the end of this week.
🎧Golden- Kpop Demon Hunters
🧬Code and notebooks will be released by the end of this week.
🎧Golden- Kpop Demon Hunters
Looks like someone has already tried to replace me with an AI agent 🫣
September 11, 2025 at 4:17 PM
Looks like someone has already tried to replace me with an AI agent 🫣
Reposted by Sergey Ovchinnikov
Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
August 27, 2025 at 4:14 PM
Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Sergey Ovchinnikov
Now that OpenCRISPR is in nature and rekindled the 'what's-a-novel-sequence' debate, I'm happy to share an app to check this, which I built for fun some time ago.
fuerstlab.shinyapps.io/SeqNovelty/
quick 🧵
fuerstlab.shinyapps.io/SeqNovelty/
quick 🧵
August 1, 2025 at 11:50 AM
Now that OpenCRISPR is in nature and rekindled the 'what's-a-novel-sequence' debate, I'm happy to share an app to check this, which I built for fun some time ago.
fuerstlab.shinyapps.io/SeqNovelty/
quick 🧵
fuerstlab.shinyapps.io/SeqNovelty/
quick 🧵
Reposted by Sergey Ovchinnikov
MMseqs2 v18 is out
- SIMD FW/BW alignment (preprint soon!)
- Sub. Mat. λ calculator by Eric Dawson
- Faster ARM SW by Alexander Nesterovskiy
- MSA-Pairformer’s proximity-based pairing for multimer prediction (www.biorxiv.org/content/10.1...; avail. in ColabFold API)
💾 github.com/soedinglab/M... & 🐍
- SIMD FW/BW alignment (preprint soon!)
- Sub. Mat. λ calculator by Eric Dawson
- Faster ARM SW by Alexander Nesterovskiy
- MSA-Pairformer’s proximity-based pairing for multimer prediction (www.biorxiv.org/content/10.1...; avail. in ColabFold API)
💾 github.com/soedinglab/M... & 🐍
August 5, 2025 at 8:25 AM
MMseqs2 v18 is out
- SIMD FW/BW alignment (preprint soon!)
- Sub. Mat. λ calculator by Eric Dawson
- Faster ARM SW by Alexander Nesterovskiy
- MSA-Pairformer’s proximity-based pairing for multimer prediction (www.biorxiv.org/content/10.1...; avail. in ColabFold API)
💾 github.com/soedinglab/M... & 🐍
- SIMD FW/BW alignment (preprint soon!)
- Sub. Mat. λ calculator by Eric Dawson
- Faster ARM SW by Alexander Nesterovskiy
- MSA-Pairformer’s proximity-based pairing for multimer prediction (www.biorxiv.org/content/10.1...; avail. in ColabFold API)
💾 github.com/soedinglab/M... & 🐍
Excited to re-share work from
@yoakiyama.bsky.social and Zhidian Zhang on MSA pairformer. (1/4)
@yoakiyama.bsky.social and Zhidian Zhang on MSA pairformer. (1/4)
August 5, 2025 at 7:39 AM
Excited to re-share work from
@yoakiyama.bsky.social and Zhidian Zhang on MSA pairformer. (1/4)
@yoakiyama.bsky.social and Zhidian Zhang on MSA pairformer. (1/4)
Reposted by Sergey Ovchinnikov
Excited to share work with
Zhidian Zhang, @milot.bsky.social, @martinsteinegger.bsky.social, and @sokrypton.org
biorxiv.org/content/10.1...
TLDR: We introduce MSA Pairformer, a 111M parameter protein language model that challenges the scaling paradigm in self-supervised protein language modeling🧵
Zhidian Zhang, @milot.bsky.social, @martinsteinegger.bsky.social, and @sokrypton.org
biorxiv.org/content/10.1...
TLDR: We introduce MSA Pairformer, a 111M parameter protein language model that challenges the scaling paradigm in self-supervised protein language modeling🧵
Scaling down protein language modeling with MSA Pairformer
Recent efforts in protein language modeling have focused on scaling single-sequence models and their training data, requiring vast compute resources that limit accessibility. Although models that use ...
biorxiv.org
August 5, 2025 at 6:31 AM
Excited to share work with
Zhidian Zhang, @milot.bsky.social, @martinsteinegger.bsky.social, and @sokrypton.org
biorxiv.org/content/10.1...
TLDR: We introduce MSA Pairformer, a 111M parameter protein language model that challenges the scaling paradigm in self-supervised protein language modeling🧵
Zhidian Zhang, @milot.bsky.social, @martinsteinegger.bsky.social, and @sokrypton.org
biorxiv.org/content/10.1...
TLDR: We introduce MSA Pairformer, a 111M parameter protein language model that challenges the scaling paradigm in self-supervised protein language modeling🧵
Reposted by Sergey Ovchinnikov
looks cool but they should really have cited and compared to gLM and gLM2, which are very conceptually similar:
www.nature.com/articles/s41...
www.biorxiv.org/content/10.1...
I'll leave a biorxiv comment for the authors. It's hard to find all prior literature but this one is kinda an oof.
www.nature.com/articles/s41...
www.biorxiv.org/content/10.1...
I'll leave a biorxiv comment for the authors. It's hard to find all prior literature but this one is kinda an oof.
August 2, 2025 at 8:01 PM
looks cool but they should really have cited and compared to gLM and gLM2, which are very conceptually similar:
www.nature.com/articles/s41...
www.biorxiv.org/content/10.1...
I'll leave a biorxiv comment for the authors. It's hard to find all prior literature but this one is kinda an oof.
www.nature.com/articles/s41...
www.biorxiv.org/content/10.1...
I'll leave a biorxiv comment for the authors. It's hard to find all prior literature but this one is kinda an oof.
PSA = Google Colab Pro free for one year for academic use (US only):
blog.google/outreach-ini...
blog.google/outreach-ini...
New Google Colab features for higher education
Google Colab offers free Colab Pro for students, interactive slideshows and AI controls in notebooks.
blog.google
July 22, 2025 at 12:33 AM
PSA = Google Colab Pro free for one year for academic use (US only):
blog.google/outreach-ini...
blog.google/outreach-ini...
Alright, last one, now I need to get back to real work... 😸
July 13, 2025 at 6:36 AM
Alright, last one, now I need to get back to real work... 😸
How metamorphic proteins change conformation. 😸
July 12, 2025 at 7:53 PM
How metamorphic proteins change conformation. 😸
Molecular cat tweezers? 😺
July 12, 2025 at 4:12 AM
Molecular cat tweezers? 😺
I think this is the best graphical abstract I've ever seen. 😍
www.cell.com/cell/abstrac...
www.cell.com/cell/abstrac...
June 18, 2025 at 4:57 PM
I think this is the best graphical abstract I've ever seen. 😍
www.cell.com/cell/abstrac...
www.cell.com/cell/abstrac...
ok, I think I broke claude 🫣
June 11, 2025 at 3:55 PM
ok, I think I broke claude 🫣