Huge thanks to the whole team: Montader Ali, Klara Kropivšek Brumat, Leonardo Salicari, Samo Miklavc, Aibek Kappassov, Chengcheng Fu, Pietro Sormanni, Ario de Marco, and Victor Greiff!

We also provide actionable guidance on sampling strategies, compute-accuracy tradeoffs, and confidence calibration relevant to pharma-facing AI biologics workflows

Our findings include:
- Confidence scores don't separate cognate and non-cognate complexes
- Geometric plausibility doesn't imply specificity
- Cross-tool agreement is weak
- Sampling improves geometry, not specificity or confidence alignment
- Compute and energy costs vary widely

We benchmarked publicly available AF3, Boltz-2, and Chai-1 across 106 experimentally solved VHH-antigen complexes and over 11,000 shuffled non-cognate pairings. We chose the VHH nanobody format for its single-domain simplicity (easy to interpreat paratope-epitope interactions)

We examined how well AI-based antibody-antigen structure prediction pipelines perform at the practical discovery-critical task of differentiating true binders from plausible but incorrect ones. Short answer: not very well.

Read the paper here: www.biorxiv.org/content/10.6...

Are you hungry? We are curious about how people think about hunger while going about their daily routine. Remember there are no right or wrong answers, there are only your answers. Responses are anonymous.

I'm doing a market research about eating habits and appetite control. Are you hungry? 🙃

If you have 2 minutes, please fill in the Google form below (anonymous, unless you want to have a follow up chat): forms.gle/Mpc86LbhGSyH...

Spread the word!

Thank you!

In 2019, we published a clustering & nomenclature of beta turns in proteins & found 18 unique types. The code was in python2. I've just rewritten it in python3, because it might still be useful to people.

The paper & code:

journals.plos.org/ploscompbiol...

github.com/DunbrackLab/...

GitHub - mqcomplab/bblean Contribute to mqcomplab/bblean development by creating an account on GitHub.

Clustering hundreds of millions of molecules in a single workstation is now a possibility!
Check the new code: github.com/mqcomplab/bb...

A compelling review of how ML/AI could help in the quest to find an enzyme for every reaction.

@jsunn-y.bsky.social @francescazfl.bsky.social Yueming Long @francesarnold.bsky.social

www.cell.com/cell-systems...

Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection Bacterial defense systems present considerable barriers to both phage infection and plasmid transformation. These systems target mobile genetic elements, limiting the efficacy of bacteriophage-based t...

Preprint: De-novo design of proteins that inhibit bacterial defenses

Our approach allows silencing defense systems of choice. We show how this approach enables programming of “untransformable” bacteria, and how it can enhance phage therapy applications

Congrats Jeremy Garb!
tinyurl.com/Syttt
🧵

Glad to share the final version of our story about the UBR4 complex, an E4 ligase protein quality control hub @science.org. Now with more cryo-EM structures and a deeper dive into substrate recognition, especially escaped mitochondrial proteins @clausenlab.bsky.social www.science.org/doi/10.1126/...

#CCPBioSim will be running their annual training week of hands-on workshops in basic biomolecular simulation techniques from the 13th-17th October, in Sheffield.

For more details, visit www.ccpbiosim.ac.uk/training2025

The registration link there will open shortly! #compchem

Degradation of Abl Utilizing an Immunoproteasome N-Degron Prodrug Targeted protein degradation is an emerging therapeutic strategy that leverages the cell’s natural protein clearance pathways to eliminate proteins of interest (POIs). One common approach involves bif...

New degrader paper using the immunoproteasome. Congrats Cody Loy and Tim Harris!
pubs.acs.org/doi/full/10....

encapsulate your target proteins for cryoEM structural determination within highly hydrophilic, structurally homogeneous, and stable protein shells 🤩

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

We're excited to present our latest article in Nature Machine Intelligence - Boosting the predictive power of protein representations with a corpus of text annotations.

Link: www.nature.com/articles/s42...
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CACHE 7 is launched with support from the @gatesfoundation.bsky.social and unpublished data from Damian Young at @bcmhouston.bsky.social, Tim Willson @thesgc.bsky.social and Neelagandan Kamaria InSTEM. Design selective PGK2 inhibitors. We'll test them experimentally.
bit.ly/4lnVYOs

3D render of a Zincore complex locking ZFP91 onto DNA, promoting gene activation. Made in Blender with Molecular Nodes.

📢 Ready for this? A new way to think about Gene Regulation!

🚨A new coregulator complex, Zincore, acts as a "MOLECULAR GRIP", stabilizing TFs at DNA binding sites across the genome!🧬

💪Proud to be part of this work led by @daaninthelab.bsky.social

Read more: science.org/doi/10.1126/science.adv2861

🚀 My first Cryo-EM structures are OUT on the PDB!

🎉Super excited about this milestone as PhD, it’s been a journey, and I’m grateful to finally have these as my first Cryo-EM structures! 🙌

🔁Thank you for sharing!❤️

Read @daaninthelab.bsky.social et. al.: www.science.org/doi/10.1126/...

⬇️ 2nd video

🚨It’s out @embojournal.org 🚨
Cardiolipin inhibits Caspase-4/11!
Huge thanks to my brilliant supervisors Kate & Pablo, to @s-burgener.bsky.social & Mercedes and all the @inflammasomelab.bsky.social, it was a joy working and laughing with you, and to @brozlab.bsky.social & Si Ming lab.

We have a new collection of protein structure generative models which we call Protpardelle-1c. It builds on the original Protpardelle and is tailored for conditional generation: motif scaffolding and binder generation.

Switching next to protein protein interactions, we used arguably my favorite protein A34F GB1 to demonstrate that these glycopolymers stabilize protein protein interactions in a similar fashion to protein folding, via chemical interactions.

Interested in solvation free energies of small molecules and proteins?

The latest @livecomsjournal.bsky.social tutorial by Egger-Hoerschinger et al provides a guide to quantifying hydration thermodynamics using Grid Inhomogeneous Solvation Theory (GIST):
doi.org/10.33011/liv...

#compchem

The Frontiers of Structure

Pushing down to the structures of ever-smaller proteins (and ever-smaller crystals!)

Happy to share the latest from the lab, led by Daniel Alvarez, in collaboration with @lizconibear.bsky.social‬. In this AA-MD tour-de-force, we delve deep into the mechanism and energetics of lipid uptake by bridge-like lipid transfer proteins, and we learn a few interesting things along the way...

Thrilled to share my first corresponding author paper as a project leader in @hillerlab.bsky.social ‪ Amazing work from first author @annaleder.bsky.social We discovered multi-chaperone condensates in the ER that revolutionise the current vision of protein folding!
www.nature.com/articles/s41...

Table of contents figure

Our latest Best Practices article "Developing Monte Carlo Methodologies in Molecular Simulations" is out now and describes how to derive acceptance probabilities for a variety of Monte Carlo moves:
doi.org/10.33011/liv...

#compchem

A benchmark dataset of 614 experimentally characterized de novo designed monomers from 11 different design studies shows that:
- deep learning structural metrics only weakly predict success
- The score distribution is different for different types of structures

@grocklin.bsky.social

Physics-based design of efficient Kemp eliminases

@lynnkamerlin.bsky.social

www.nature.com/articles/s41...

All all-atom diffusion model of protein sequences.

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

Very excited about our latest all-atom generative model proteina, check out the project page (research.nvidia.com/labs/genair/...) and stay tuned for the code release soon!