I'm excited to share that I'll be joining @MITBiology as an Asst Prof. in Jan 2024! Come join us! 🤓🧪🖥️🧬

🚀 Excited to share BindClaw! 🦀

Starting from a prompt or research paper, BindClaw connects biological mechanisms to protein design: identify targets and binding sites → build mechanism-specific computational assays → generate and assess binders → refine designs using the to evaluate whether designs fit the intended biological objective, including competition with a native partner and preference for a particular molecular state. 🧬

In a human-guided calmodulin campaign, 15 of 18 designs showed binding to calcium-loaded CaM, including subnanomolar binders supported by both BLI and SPR.

This work is an incredible team effort together with @DidiKieran , @saint__ai, @ Kyle Gion and @sacdallago and many others!

📄paper/project: research.nvidia.com/labs/dbr/asset…
💻code: will be released in a few weeks!

Someone using ai agents to improve @biorxivpreprint website? 😅

Avengers assemble: 1 year BakerLab + NVIDIA GenAIR = 🔥 rfd4-proteina.org

Presenting RFD4-Proteina, our latest protein design model, significantly better and faster than everything we compared against, both in silico and in the lab! 1/30

🧪 @UWproteindesign + 💚 NVIDIA = 👶 RFD4-Proteina

Proud parents ✨ Gifted kid

Today we are excited to release Artios, a fully open source system for designing functional de novo enzymes.

Enzymes present a new frontier for de novo protein design models due to the challenge of coordinating precise chemistry, rather than binding a target.

Enzymes are life’s by designing them we can truly start to engineer biology.

We believe these fundamental capabilities should be built in the open and shared with the community to progress science faster.

🧵 1/6

Public preview of BioEmu2! @MSFTResearch AI for Science’s new foundation model for biomolecular structure, dynamics and function. Open weights, MIT license.
github.com/microsoft/bioe…

Movie: BioEmu2-simulated binding of intrinsically disordered peptide PUMA to MCL-1 receptor. 🧵⬇️

Generative protein design is transforming macromolecular drugs, but de novo designed therapeutics could still be hindered by immunogenicity in the clinics. Excited to introduce MESSI, a discrete diffusion model for generative protein deimmunization.

BindCraft2 v1.0.4 has been released: with significantly improved VHH, scFv, ARP, and induced fit targeting. WE also improved speed and code stability. Try your difficult campaigns again. Great work by Erik Mäeots, Leonardo Tredese and Elizaveta Chernova.

Protein immunogenicity is a major driver of drug failure in the clinic, a problem especially important in the age of generative AI when we can design de novo medicines with desired function.

Meet 🐐MESSI: a generative method for deimmunizing proteins with discrete diffusion. We epitopes and experimentally validate retained or improved function in luciferases, PD-1 binders and uricases—an enzyme family used in FDA-approved therapies.💊

Watch the story below:
1/n 🧵

Come join us 🤗

Most important, we want to get this model into as many scientists’ hands as we can.

Today, we’re announcing that 10,000 scientists will get the highest usage tier access to Gemini 4 Argon in Google @antigravity free of charge for 6 months.

Apply here: forms.gle/WvmBbPvRbpKG1B…

This is 3rd time I heard of someone not getting tenure for their Nobel Prize winning work.

Seems if you aren't on the verge of NOT getting tenure, you aren't doing Nobel Prize worthy work? 🙃

Anyone have access to free AMD gpus they aren't using? Was gonna try test some ported methods but dont have access to any AMD gpus to test on.

I have postdoc positions available to lead two new exciting projects! One is on in situ protein sequencing (collab with Ed Boyden at MIT) and the other is on modeling cryptic pockets for drug discovery (collab with Scripps and MGH). Reach out if interested! Details below

Introducing AlphaProtein Novo, a pipeline for de novo enzyme design! In collaboration with @francesarnold's group, we developed AP Novo and used it to get SoTA "novel-scaffold" activity on 2 benchmark reactions and create enzymes to synthesize the pharmaceutical motif piperidine mental toxin DEHP.

Work led by @ZvxyWu @ZiqiLi0513 with teammates @alexechu_ @kelly_ruijie @schulluc @jacobjinkelly @rosaliags @davidla @solserpens @j_reisenbauer, @pengliu_group, Josh, Thomas, Amy, Tristan, Harshnira, and others. It was a joy and privilege to work with you all!

Preprints and code:
biorxiv.org/content/10.648…
biorxiv.org/content/10.648…
github.com/google-deepmin…

When do biological reasoning models use their biological inputs?

High performance can create a mirage of reliance on biological representations. Reasoning traces don’t always reflect the evidence.

Our paper examines these limits and paths to better biological reasoning models.

Getting ready for today... 😅

Can genomic language models design biological systems to access new regions of chemical space?

Some of the most complex molecules in nature are made by biosynthetic gene clusters: massive enzymes that carry out complex chemistry. But engineering these systems is challenging due interactions. To solve this, we applied gLM2 to controllably generate new domain architectures by learning from vast evolutionary data.

Genomes are full of dark matter of unknown functions.

We present Minerva, a new method for discovery guided by genome language models. Minerva reveals the interactions hidden in non-coding DNA, pointing to hundreds of new putative RNAs and repetitive elements per bacterial us to find and study elements invisible to traditional methods at orders of magnitude greater scale than before.