MFW you have an awesome idea and need to pull up a random biorxiv paper for critical details

Not sure how to reconcile A) bindcraft consistently outperforming RFDiffusion, but B) AF3-gen diffusion-based design outperforming AF3-gen hallucination-based design. My best guess is that there's something about AF2 but not AF3-gen methods that makes them amenable to backprop?

New latent labs report on de novo antibody design closely follows what we’ve seen from Chai and Nabla. Promising results, and I respect that they admit that half of the targets were unsuccessful with their approach www.latentlabs.com/wp-content/t...

Here is Claude Opus's attempt at one-shot refactoring the PyTorch implementation of ProteinMPNN. Impressive work, but it could be better github.com/delalamo/Pro...

Folding funnels are back - now we just need to convince scientists to resume using P_near, a funnel-ness metric that deserved far more use than it received

has anyone found a workaround for dealing with unrealistically overstructured loops being generated by Boltz/chai/etc? It’s an annoying problem that forces me to default to prior-gen NNs for a lot of human proteins

Happy to share our cryoEM Ensemble Optimization method! 🎉It infers optimal structures and their weights directly from individual cryoEM images - no maps just physics! with David Sliva-Sánchez, @erikhthiede.bsky.social & Roy Lederman www.biorxiv.org/content/10.6...

Another advertisement for an antibody design company masquerading as a paper with opaque, non-reproducible methodology

A randomly valuable thing that the simplefold authors did was fine-tune all six structure prediction models on MD-ATLAS data, and honestly I can't tell if there's any benefit to scaling these things if the goal is ensemble prediction

Has this idea of sampling neighbors from an inverse cubic distribution been used in protein structure GNNs at all since the idea was first presented in the Chroma paper ~3 years ago? I thought it was incredibly clever and expected it to catch on, but haven't seen it since

Biomolecular diffusion models aren't able to reproduce the equilibrium dynamics of the simulations they're trained on arxiv.org/pdf/2506.17139

Very cool paper that samples unique conformations by adding a guidance term to diffusion-based protein structure prediction to steer away from already-sampled states. Important caveat: doesn't work with mAbs because it only looks at helices and sheets openreview.net/pdf/dd8aa97e...

An absolutely fascinating edge case from BoltzGen: apparently it loves to design ubiquitins, but only when the prompted sequence is 73-76 AAs long! Reminds of a method from Possu Huang's group (forget which) that designed TIM barrels with lots of enthusiasm

Why do inverse folding methods hate aromatics so much? From the BoltzGen paper

Boltz is now a separate institution? ...

Excited to release BoltzGen which brings SOTA folding performance to binder design! The best part of this project is collaborating with a broad network of leading wetlabs that test BoltzGen at an unprecedented scale, showing success on many novel targets and pushing the model to its limits!

A class like no other!! From #AI structure hallucination 🤖 to #CryoEM structure reality 🔬 by @biozentrum.unibas.ch @unibas.ch undergraduate students👩‍🔬👩‍🎓 in just a few weeks! One of their creations is this beautiful flower-shaped tetrameric pore 🌼, a brand new member of the #ProteinCosmos 🧶🧬 🧪

Hmmmm..... wonder what @opig.stats.ox.ac.uk is up to... github.com/oxpig/HeavyB...

Where can I find thousands of bovine antibody sequences with ultra-long CDR3s? Preferably paired 🧶🧬

Love this preprint and glad to see the field converge on a specific, highly descriptive term for this phenomenon

New job! Senior scientist in AI/ML at Takeda. The plan is to do some fun stuff with biomolecular foundation models

If you've been including PDB 9DMQ chain F with ANARCI/AbNum-derived numbering in your training set for learning something like CDR design, then you'll be surprised to learn that the CDRH3 is only 7 AAs long and encompasses exclusively the region in green opig.stats.ox.ac.uk/webapps/sabd...

Does anyone know how IMGT numbers residues in the DE loop (residues 80-84)? I can't figure out the pattern, seems to be more or less entirely random and not following the logic of CDR1-3

The entire J-gene of PDB 7czv (3.3 Å, shown in salmon) seems to have fallen victim to a register/misassignment error, with the C-terminal valines (right) and tryptophan (center-left) on the wrong side of the beta sheet compared to where they would be expected to be

I've put together a tool to renumber antibody structures using only main chain atomic coords. No sequence info is used at all. In the process I found a few numbering mistakes in Sabdab/PDB, which is numbered by sequence & thus sensitive to gaps/register errors (deleted prev post due to bugs)

I flirted with doing something like this a year or two ago - prepending a mAb-specific structure prediction NN to the AF2 template input for mAb design by hallucination - but was stopped by the fact that every Bio/ML NN is in PyTorch except AF2 which is written in freaking JAX

One mo'

It's a very cool result but IMO there are caveats. Inference is (mostly) slower. There is existing work on faster models (e.g. MiniFold or protenix mini), and also existing work on ensemble prediction. I doubt this works without training on AFDB, which bakes in inductive bias from triangle layers

Still boggles my mind that we can leave frameworks as-is and only edit CDRs and still reliably get nM binders. Complete opposite of what I would have expected given how hard it is to graft CDRs from one FW to another (such as humanizing mouse mAbs). First RFantibody and now this

Postdoc position available in the BioEmu team at @msftresearch.bsky.social AI for Science - Berlin DE or Cambridge UK. Looking for candidates with backgrounds in #MachineLearning #AI Biophysics or Bioinformatics jobs.careers.microsoft.com/global/en/jo...

Apple now has a protein folding NN?... arxiv.org/pdf/2509.18480

How to request your swiss criminal record: 1. Fill out a form online 2. Pay a processing fee, also online 3. Print form and put it in an envelope and MAIL it 4. Receive criminal record by email

The only thing more compelling than this preprint's science are the names of some of its authors

This upcoming week is my last week at GSK. I’m going to move on to greener pastures but first a few weeks off to … close on a house! Go for some bike rides! Paint 40k models! Etc.!

Yep. Reminds me of the bar plot error bars that were just capital Ts

Protein language models can predict epistasis (non-additivity of multiple point mutations) if predictions are nonlinearly transformed first www.biorxiv.org/content/10.1...

I posted this on the other site and will repost here: something is fishy with Fig 2F results on inverse folding performance (left). Variance is way too low. Compare that to my results preprinted earlier this year (right). Definitely causing me to scrutinize other results in this paper more closely

Does anyone know of an NN-based drop-in replacement for protein side chain repacking (e.g., Rosetta repack/SCWRL)? Ideally something lightweight

New review on computational design of intrinsically disordered proteins 🖥️🍝 by @giuliotesei.bsky.social @fpesce.bsky.social & 👴 doi.org/10.48550/arX...

Structural bioinformatics is incredibly powerful on its own or when paired with theory or experiment. One of the PDB's superpowers isn’t from one structure, but comparing many to uncover folds, binding sites, and subtle conformational shifts. chemrxiv.org/engage/chemr...

Time to test their claim that diffusion is competitive with hallucination in generating realistic backbones of huge (>800 AA) proteins...

The journal version of "Biophysics-based protein language models for protein engineering" with @philromero.bsky.social is live! Mutational Effect Transfer Learning (METL) is a protein language model trained on biophysical simulations that we use for protein engineering. 1/ doi.org/10.1038/s415...

Can anyone familiar with the economics of this situation explain how UK salaries can be 1/3 of US salaries, yet the UK is still described as being more unfriendly for R&D than the US, even when the quality of the work being done is largely the same?

I'll be presenting some of our ongoing work on the use of protein design to enable cryo-EM of challenging transmembrane drug targets at the Discovery on Targets conference in Boston on September 24. Come say hi!

Update: RareFold 🧬 Our AI framework for protein design with 29 noncanonical AAs now shows designed binders (linear + cyclic) are non-immunogenic in patient-derived assays — paving the way for safe next-gen peptide therapeutics. 👉https://www.biorxiv.org/content/10.1101/2025.05.19.654846v2

Boltz v2.2.1 out. A few improvements including support for .pdb templates, better treatment of stereochemistry in guidance potentials, and improved documentation. As always a great thank you to all those in the community who contributed via PR, raising issues or directly reporting issues to us.

An analysis of scaling laws in paired antibody LMs, which mostly learn the composition of germline sequences. Authors conclude that an 650M parameter NN (the sweet spot for generalist PLMs) would require 5.5 M sequences, about ~3x what is publicly available today www.biorxiv.org/content/10.1...

In the CASP16 category examining modeling of multiple conformational states, "no one group dominated in these performance rankings across all targets." Server-based methods in particular were quite mediocre

Excited to launch our 1st Antibody Developability AI competition today on huggingface! Show off your model’s ability to predict developability of Abs - most common request we get from biopharmas! And win $60K in prizes😄 Excited to do more of these at Ginkgo huggingface.co/spaces/ginkg...

I wonder if there are scientists who keep a running list of urgent scientific questions that are currently unanswerable due to technological limitations, & whether the innovation required in such cases overlaps at all with the products being released on an almost weekly basis now