Tristan Bepler
tbepler.bsky.social
Tristan Bepler
@tbepler.bsky.social
Scientist and Group Leader of the Simons Machine Learning Center
@SEMC_NYSBC. Co-founder and CEO of http://OpenProtein.AI. Opinions are my own.
Pinned
Excited to share PoET-2, our next breakthrough in protein language modeling. It represents a fundamental shift in how AI learns from evolutionary sequences. 🧵 1/13
Our preprint on sequence-to-property learning and zero-shot fitness prediction with PoET-2 is live: arxiv.org/abs/2508.04724

PoET-2 is also open sourced on github: github.com/OpenProteinA...

Thanks to the @openprotein.bsky.social team!
Understanding protein function with a multimodal retrieval-augmented foundation model
Protein language models (PLMs) learn probability distributions over natural protein sequences. By learning from hundreds of millions of natural protein sequences, protein understanding and design capa...
arxiv.org
August 26, 2025 at 3:39 AM
Reposted by Tristan Bepler
Boltz-1 & Boltz-2 now live via GUI & APIs! Predict protein, protein–RNA/DNA/ligand structures with confidence scores & binding affinity metrics for virtual screening. Compare finetuned models in the new overview page to find your best performer fast.
www.openprotein.ai/early-access...
July 25, 2025 at 5:18 PM
Reposted by Tristan Bepler
Product update: Indel Analysis lets you score insertions/deletions across your sequence using PoET-2. You can now also compare multiple 3D structures in Mol* to evaluate design alternatives.
Sign up now: www.openprotein.ai/early-access...
June 25, 2025 at 5:14 PM
Why does no one in AI protein engineering work on indels?

We’re solving this at OpenProtein.AI. Check out our upcoming indel design tool! 🤩 1/4

@openprotein.bsky.social
June 20, 2025 at 4:50 AM
Reposted by Tristan Bepler
Have we hit a "scaling wall" for protein language models? 🤔 Our latest ProteinGym v1.3 release suggests that for zero-shot fitness prediction, simply making pLMs bigger isn't better beyond 1-4B parameters. The winning strategy? Combining MSAs & structure in multimodal models!
May 8, 2025 at 12:29 AM
Reposted by Tristan Bepler
Product update: PoET-2 now supports structure inputs for enhanced prediction and design via Python APIs. Check out our new inverse folding tutorial to see it in action.
🔗 docs.openprotein.ai/walkthroughs...

Sign up for OpenProtein.AI: www.openprotein.ai/early-access...
Inverse Folding with PoET-2 for Generation of Novel Luciferases — OpenProtein-Docs documentation
docs.openprotein.ai
May 13, 2025 at 3:28 AM
Generative protein sequence design, variant effect prediction, and fine-tuning are now fully supported for PoET-2 with structure and sequence prompts in the @openprotein.bsky.social python client and APIs!

Check out our new walkthrough on inverse folding: docs.openprotein.ai/walkthroughs...
Inverse Folding with PoET-2 for Generation of Novel Luciferases — OpenProtein-Docs documentation
docs.openprotein.ai
May 12, 2025 at 4:17 PM
Reposted by Tristan Bepler
🧬 Protein Revolution: The Tiny Model Making a Massive Impact!
PoET-2 is changing the game in computational protein design, slashing experimental data needs by 30x! 🚀

learn more: www.synbiobeta.com/read/protein...

#ProteinDesign #BiotechInnovation #AIRevolution
Protein Revolution: The Tiny Model Making a Massive Impact - SynBioBeta
www.synbiobeta.com
February 21, 2025 at 12:19 AM
Excited to share PoET-2, our next breakthrough in protein language modeling. It represents a fundamental shift in how AI learns from evolutionary sequences. 🧵 1/13
February 11, 2025 at 2:30 PM
Reposted by Tristan Bepler
🧬 Announcing PoET-2: A breakthrough protein language model that achieves trillion-parameter performance with just 182M parameters, transforming our ability to understand proteins.
February 11, 2025 at 1:38 PM
Reposted by Tristan Bepler
Can we learn protein biology from a language model?

In new work led by @liambai.bsky.social and me, we explore how sparse autoencoders can help us understand biology—going from mechanistic interpretability to mechanistic biology.
February 10, 2025 at 4:12 PM
Reposted by Tristan Bepler
A flexible framework for fast and accurate segmentation of filaments and membranes in tomograms and micrographs - the TARDIS manuscript is now live
@biorxivpreprint.bsky.social !

Thanks to hard work by Robert Kiewisz and our many collaborators!

www.biorxiv.org/content/10.1...
Accurate and fast segmentation of filaments and membranes in micrographs and tomograms with TARDIS
It is now possible to generate large volumes of high-quality images of biomolecules at near-atomic resolution and in near-native states using cryogenic electron microscopy/electron tomography (Cryo-EM...
www.biorxiv.org
December 21, 2024 at 4:00 PM
I'll be talking about shrinking protein language models with #PoET and protein engineering at openprotein.ai tomorrow at A*STAR's Bioinformatics Institute.

If you can't make it, I'll also be presenting at the Berger Lab seminar @mitofficial.bsky.social on Wednesday!
December 1, 2024 at 3:09 PM
Reposted by Tristan Bepler
Yet more evidence that transfer learning of sequence-only PLMs does not benefit from scale beyond 650M params 🧵
November 25, 2024 at 7:34 AM