Diego del Alamo
@delalamo.xyz
Computational protein engineering & synthetic biochemistry at Takeda
Opinions my own
https://linktr.ee/ddelalamo
Opinions my own
https://linktr.ee/ddelalamo
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
December 8, 2025 at 3:16 PM
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
Reposted by Diego del Alamo
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...
Cryo-electron microscopy ensemble optimization using individual particles and physical constraints
Biomolecules are inherently dynamic, and understanding their conformational ensemble distributions is essential for understanding their dynamics and biological roles. Cryo-electron microscopy (cryo-EM...
www.biorxiv.org
December 5, 2025 at 4:13 PM
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
Drug-like antibody design against challenging targets with atomic precision https://www.biorxiv.org/content/10.1101/2025.11.29.691346v1
December 1, 2025 at 9:52 PM
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
November 17, 2025 at 3:22 PM
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
November 16, 2025 at 9:01 PM
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
November 14, 2025 at 3:37 PM
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...
openreview.net/pdf/dd8aa97e...
November 7, 2025 at 6:29 PM
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...
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
October 27, 2025 at 5:03 PM
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
October 27, 2025 at 3:36 PM
Why do inverse folding methods hate aromatics so much? From the BoltzGen paper
Boltz is now a separate institution? ...
October 27, 2025 at 1:19 AM
Boltz is now a separate institution? ...
Reposted by Diego del Alamo
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!
October 26, 2025 at 10:40 PM
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!
Reposted by Diego del Alamo
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 🧶🧬 🧪
One of their creations is this beautiful flower-shaped tetrameric pore 🌼, a brand new member of the #ProteinCosmos 🧶🧬 🧪
October 26, 2025 at 1:48 PM
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 🧶🧬 🧪
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...
GitHub - oxpig/HeavyBuilder2: A web app for HeavyBuilder2
A web app for HeavyBuilder2. Contribute to oxpig/HeavyBuilder2 development by creating an account on GitHub.
github.com
October 24, 2025 at 12:24 PM
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 🧶🧬
October 22, 2025 at 12:17 PM
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
October 14, 2025 at 5:57 PM
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
October 13, 2025 at 8:59 PM
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...
October 9, 2025 at 12:39 PM
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
October 8, 2025 at 7:25 PM
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
October 6, 2025 at 8:41 PM
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)
GitHub - delalamo/SAbR: Structure-based antibody renumbering
Structure-based antibody renumbering. Contribute to delalamo/SAbR development by creating an account on GitHub.
github.com
October 4, 2025 at 10:28 PM
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
mBER: Controllable de novo antibody design with million-scale experimental screening [new]
Ab design via seq/struct conditioning designs VHHs. Million-scale screens show success.
Ab design via seq/struct conditioning designs VHHs. Million-scale screens show success.
September 29, 2025 at 10:09 PM
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'
mBER: Controllable de novo antibody design with million-scale experimental screening
Recent machine learning approaches have achieved high success rates in designing protein binders that demonstrate in vitro binding to their targets. While open models for unconstrained "minibinder" de...
www.biorxiv.org
September 29, 2025 at 7:42 PM
One mo'
Reposted by Diego del Alamo
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
September 26, 2025 at 6:00 PM
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
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.
Germinal produces functional nanobodies in just dozens of tests, making custom antibody design more accessible than ever before.
September 25, 2025 at 2:07 AM
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
Reposted by Diego del Alamo
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...
jobs.careers.microsoft.com/global/en/jo...
September 24, 2025 at 1:06 PM
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...
jobs.careers.microsoft.com/global/en/jo...