@btnaughton.bsky.social's VHH competition results are out! There were two entrants: me and Brian. We both lost

Do you have modal.com credits you need to light on fire? Do you want to feel like a hacker while vibe designing protein minibinders? Try running `uvx --from 'mosaic-tui @ git+https://github.com/escalante-bio/mosaic-tui mosaic --pdb 1ubq` from your terminal. No need to install anything.

Teaching generative models to hallucinate There are currently two main approaches to computational protein binder design: optimization (exemplified by BindCraft) and generative models (e.g. BoltzGen). A design campaign using either method l...

New post: blog.escalante.bio/teaching-gen.... You can massively improve in silico metrics for BoltzGen using standard post-training techniques (with a structure model as your reward function). If this holds up (no wetlab testing yet!) you could get binders in seconds rather than hours...

How to Design Antibodies A step-by-step guide to making de novo binders.

I wrote a primer on AI antibody design, published on Asimov press.

www.asimov.press/p/antibody-d...

Toward universal binder discovery: Advances in display, computational design and in vivo platforms Protein binders are fundamental tools in chemical biology, key components of biotechnologies, and the foundation of biologics-based medicines. However…

Check out our new review on binder discovery! In a fast-moving world, here are some thoughts we have in the moment.

Congrats @jzy2799.bsky.social and Eddy!!

www.sciencedirect.com/science/arti...

sometimes I wonder if Claude Code really does make me more productive. sure, it implemented this much faster than I could have, but I probably would have had the sense not to...

Excellent, comprehensive rundown of the state of bio lab automation by @owlposting1.bsky.social

In retrospect, it's an important topic that has had almost zero discussion over the years!

A fun surprise to see some decade-old(!) work show up in there too.

www.owlposting.com/p/heuristics...

Developability comes for free...? Did AI de novo antibody generation models learn developability properties without explicitly being trained on this?

Great piece on antibody developability in the AI era by Adil Yusuf
ayusuf.substack.com/p/developabi...

github.com/adaptyvbio/p...

Very cool Claude skills for protein design from x.com/CotetTudor and Adaptyv.

Their standard pipeline should enable anyone (+Claude) to easily design binders at close to state of the art!

I'm happy to see it uses my biomodals repo in parts github.com/hgbrian/biom...

Tudor-Stefan Cotet (@CotetTudor) / X Tudor-Stefan Cotet (@CotetTudor) / X

Very cool Claude skills for protein design from x.com/CotetTudor and Adaptyv.

Their standard pipeline should enable anyone (+Claude) to easily design binders at close to state of the art!

I'm also happy to see it uses my biomodals repo in parts github.com/hgbrian/biom...

~180 lines of code to win the in silico portion of the Adaptyv Nipah binding competition Here's the script we used to get 1st place in the in silico portion of the Adaptyv Nipah competition: import modal def download_boltz2(): from mosaic.models.boltz2 import Boltz2 Boltz2() ...

finally wrote up some notes on the adaptyv competition: blog.escalante.bio/180-lines-of....

Blogpost: I took an oral probiotic for a month and did microbiome sequencing at @Plasmidsaurus.

blog.booleanbiotech.com/oral-microbi...

Releasing alignism, a small tool that I have found useful for doing multiple sequence alignment in browser.

hgbrian.github.io/alignism/

- The hard work was done by the awesome biowasm team!
- Does tree building too
- V fast compared to e.g., muscle on EBI
- Not tested that much!

Great! If each student signs up for modal you'd get $$$ in free compute.

GitHub - hgbrian/foldism: protein folding app running on modal protein folding app running on modal. Contribute to hgbrian/foldism development by creating an account on GitHub.

I semi-vibe coded a frontend for all the protein folding tools I've been running. It runs on modal and has 5 different open-source algorithms: Chai1, Boltz2, AF2, Protenix(-mini).

Not 100% polished but hopefully of use to some use to people in the field!
github.com/hgbrian/fold...

I wrote up a short blogpost on using Claude Code / Opus 4.5 for computational biology

blog.booleanbiotech.com/claude-code-...

I was conserving characters but Sally Smith Hughes wrote “Genentech: The Beginnings of Biotech”

A treasure trove of biotech and early SV oral histories by Sally Hughes: digicoll.lib.berkeley.edu/search?p=%28...

Genentech (Boyer, Goeddel (recommended!)), VC (Byers, Rock, Valentine), Kaiser ("History of the Kaiser Permanente Medical Care Program"), Lilly, Paul Berg, Stan Cohen, lots more.

I’ve been testing BoltzGen a bit recently and while I haven’t done any experimental testing yet, the quality of the software is very clear. It installs, runs, logs everything, has tons of options. Very excited to test out the designs irl!

I decided to experiment with my own (small) protein design competition!

It's specifically to test how well VHH pipelines work for binder design, without the usual careful tuning.

You submit a modal script, I run it and test on benchbb.bio

blog.booleanbiotech.com/vhh-competit...

Pretty interesting that AFAICT the filtering was done after the fact (so, library 1 had no filtering). This could make it an excellent dataset for training/testing filters/rankers. Too bad it looks like the dataset is not public

Another promising VHH model just dropped today from Manifold Bio. This one builds on BindCraft and ColabDesign. MIT license!

www.biorxiv.org/content/10.1...

The success rates appear to be lower than other tools, but this is highly target-dependent.

New blogpost on the latest in AI antibody design.

Including some code to easily run Germinal and IgGM on modal!

blog.booleanbiotech.com/ai-antibody-...

It has been interesting to use gitingest to paste entire codebases for new tools into Gemini and ask for severe bugs (logic, incorrect variables...).

I think it found at least one this morning. I have to double-check before filing but it's a real bug from what I can tell...

In another preprint from the @brianhie.bsky.social Lab and @synbiogaolab.bsky.social, they introduce Germinal, a generative AI system for de novo antibody design.

Germinal produces functional nanobodies in just dozens of tests, making custom antibody design more accessible than ever before.

A REALLY nice use of nanobanana (Gemini) is cleaning up blurry old images. Of course it depends what you ask for, but it is amazing at keeping the text and content the same.

We decided to try to 3d print custom chess pieces.

The workflow of asking gemini to iterate on a design image, then uploading that image to adam.new worked amazingly well. 5 minutes work!

Left is the gemini image and right is the mesh.

I was reminded about Blackett's War by a mention on the @patio11 podcast. Terrific book about operations research / probability theory applied to real world problems.

Lots of anecdotes like this...

Recently tested some de-novo minibinders against two targets (thanks Adaptyv!) designed using our open-source design library, `mosaic`; our best method got hit rates of 7/10 and 8/10 and affinities as low as single-digit nanomolar. Wrote up some thoughts here: blog.escalante.bio/minibinder-d...

Ibex from Prescient Design arxiv.org/abs/2507.09054 github.com/prescient-de...

- antibody folding with performance like Boltz/Chai but up to 100X faster
- does not fold the complex, just the antibody
- predicts holo and apo forms
- sadly, model weights are not freely available