Ernst Schmid

AlphaFold Database is expanding into pandemic preparedness. Together with NVIDIA, DeepMind, EBI et al. we exhaustively predicted ~1.7 million homo- & heterodimers across 2,812 viral proteomes, resulting in 8,028 high-confidence predictions. 📄 research.nvidia.com/labs/dbr/ass... 🌐 alphafold.ebi.ac.uk

AlphaFold2-WebGPU now supports AlphaFold-Multimer. As in ColabFold, simply use : to separate chains in the sequence input. It is also becoming much more stable: I was able to predict a 491-aa protein in ~4 minutes in M4 Pro. Chrome currently performs better than Firefox for WebGPU, unfortunately.

Structural basis for nutrient-activated channel opening in bacterial spore germination receptors https://www.biorxiv.org/content/10.64898/2026.08.27.747515v1

This is now published! For those interested in microbial mechanotransduction: www.cell.com/current-biol...

🧬 How is MCM2-7 switched on? Our paper shows DDK phosphorylation exposes Sld3-binding sites on Mcm4/Mcm6. Sld3-Cdc45 then delivers Cdc45 to Mcm2/Mcm5, driving CMG assembly. In summary, our work explains why MCM2-7 phosphorylation is needed to turn on replication. www.nature.com/articles/s41...

Most PDB structures report one set of coordinates. But the experimental data behind them, in both X-ray crystallography and cryo-EM, is produced by an ensemble of structures. How to extract this ensemble data at scale has been a quest in structural biology for 40+ years.

Thanks very much to the @kempnerinstitute.bsky.social for supporting our work! I’m excited to see what we will learn about cell biology of the synapses by modeling pairs of synaptic proteins that interact in BioPlex. Congratulations also to all the other award recipients!

Five years ago, the #AlphaFold Database, a collaboration with Google DeepMind, made predicted protein structures free for everyone to use. Today, the database contains over 260 million structure predictions and is used by more than 3.5 million researchers in 190 countries around the world.

Another chapter of my thesis is out! We asked whether we could pair proteome-wide AlphaFold screening with Tn-seq to identify biologically relevant protein-protein interactions. We identify ClcR (formerly YerH) as a component of the Rod complex in Gram-positive bacteria. www.pnas.org/doi/10.1073/...

Does your designed active site already exist in nature? Is an uncharacterized protein hiding a catalytic site or a pocket? Folddisco answers both, searching millions of structures for a 3D motif in seconds. @natbiotech.nature.com 🧬 📄 www.nature.com/articles/s41... 🧵1/7👇

Introducing nail - a Rust implementation of profile HMM sequence alignment for proteins. Near-HMMER sensitivity, but a lot faster: www.biorxiv.org/content/10.1... github.com/TravisWheele...

My latest work! We found that the autoproteolytic GAIN domain which mediates force responsive signaling in adhesion GPCRs is not unique to eukaryotes. The microbial counterparts anchor diverse adhesion, enzymatic, and toxin domains to the cell surface, enabling release by likely mechanical stimuli.

Microbial GAIN domains undergo autoproteolysis and enable release of diverse cell surface associated proteins https://www.biorxiv.org/content/10.64898/2026.05.12.724683v1

Now published in NSMB! Paper: doi.org/10.1038/s415... Full PDF: rdcu.be/fhBtI Overview of additions since the preprint👇 (1/5)

Ph.D. finished! So many people to thank (pictured) but especially B. subtilis (& S. aureus & B. anthracis) (not pictured)

CSS nesting is now Baseline 🎉 Write nested selectors directly in CSS — just like Sass, but natively. .card { color: black; &:hover { color: blue; } .title { font-weight: bold; } } No preprocessor needed. Learn more 👇 developer.mozilla.org/en-US/docs/...

AlphaFold database has entered the era of complexes. Together with NVIDIA, DeepMind and EBI, we use ColabFold, OpenFold and MMseqs2-GPU to predict ~31 million complexes (homo & hetro-dimers) resulting in 1.8 million high-quality predictions 📄 research.nvidia.com/labs/dbr/ass... 🌐 alphafold.ebi.ac.uk

Fer’s tour de force in B. anthracis is out! Fer got Tn-seq running, built an ordered knockout library, defined all essential sporulation genes, and found a peptidoglycan deacetylase inhibitor critical for engulfment. Including our first one-by-all Alphafold screen! journals.plos.org/plosbiology/...

How to keep in step when your (protein) partner speeds up… Here we investigated the adaptive remodeling of a protein-protein interaction surface essential for telomere protection. Congrats to whole team! www.science.org/doi/10.1126/...

Online now: A metabolic atlas of mouse aging

Protein domains have no single definition, so why stick to one segmentation? 🧩 Instead of forcing structures into rigid classifications, we built AFragmenter. It uses AlphaFold PAE networks for a tuneable approach to domain parsing. You control the granularity. 👇 🔗 doi.org/10.1093/bioi...

Our lab is seeking a Postdoctoral Fellow. The position is intentionally broad, as we are looking for outstanding researchers from diverse scientific backgrounds to advance our understanding of cilia and ciliopathies: academicpositions.harvard.edu/postings/15526

End-to-end protein design in the browser through evedesign. Generate and interactively explore designs in 2D/3D and export them as codon-optimized DNA. The underlying open source framework (released soon) is build to easily add new methods, more on that soon. 🌐 evedesign.bio

Martin Filipovski successfully defended his PhD thesis today! Congrats, Dr. Filipovski.

If you use Boltz1/2, BioEmu, Chai1, or other MSA-dependent models, you’re likely using our ColabFold server. Please be considerate! Avoid large submissions across many IPs instead generate the MSA locally. Our server is an old-timer from 2014 and can’t handle that load.

Great talk by @sami-c.bsky.social about the proper use and caveats of AlphaFold2/3 predictions, highly recommended to watch www.youtube.com/watch?v=z7vy...

Unexpectedly, @jurgjn.bsky.social found that running Alphafold3 predictions for protein interactions can yield ipTM scores that are more predictive of true interactions when run in pools of proteins instead of pairwise predictions. Presumably, this reflects some sort of "competition effect".

Folddisco finds similar (dis)continuous 3D motifs in large protein structure databases. Its efficient index enables fast uncharacterized active site annotation, protein conformational state analysis and PPI interface comparison. 1/9🧶🧬 📄 www.biorxiv.org/content/10.1... 🌐 search.foldseek.com/folddisco

Our AlphaFold 3 prediction analysis tool is now accepting the new version of the AlphaFold 3 server output files. Thanks to those who let me know about the output change and apologies for any inconvenience! predictomes.org/tools/af3/

Very happy to share that a large part of my thesis work is out today: B. subtilis uses the second messenger c-di-AMP to modulate its turgor pressure in response to the state of its cell envelope. www.nature.com/articles/s41...

Excited to share that our EndoMap project is now out! A fun collaboration with Miguel Gonzalez-Lozano from the @harperlabhms.bsky.social. Explore our #AlphaFold structural interactome of #XLMS complexes in endosomes-> endomap.hms.harvard.edu and read about it here-> www.nature.com/articles/s41...

Last week I learned that all my NIH awards were terminated due to perceived acts of antisemitism by Harvard. My understanding (which may be incorrect) is that this has been extended to literally every grant to grad students, postdocs and faculty throughout the university.

Read all about Apoorva Baluapuri’s new work on Integrator (INT) in HMS News! @baluapuri.bsky.social @adelmanlab.bsky.social tinyurl.com/y2fx22c2

 🧬🎉Thrilled to share our new chromatin remodeling study! We reveal three states of human CHD1 and identify a novel "anchor element" that interacts with the acidic patch—conserved among remodelers. Our structures clarify mechanisms of remodeler recruitment! Link: authors.elsevier.com/a/1l2ik3vVUP...

Super excited to share a new preprint from our lab on design of small-molecule binding proteins using neural networks! The paper has a bit of everything. A new graph neural network, new design algorithms, and experimental validation. www.biorxiv.org/content/10.1... 🧵🧪

How do cells achieve an optimal mitochondrial distribution? Excited to share a piece of this puzzle: www.science.org/doi/10.1126/...

🔬 New from the Farnung Lab: We established a fully in vitro reconstituted chromatin replication system and report the first cryo-EM snapshots of the human replisome engaging nucleosomes. Brilliant work by @felixsteinruecke.bsky.social with support from @jonmarkert.bsky.social! tinyurl.com/replisome

It has been coming a long way... happy to share our latest work with you: www.biorxiv.org/content/10.1... Here, we show the importance of septal fortification by the Class A Penicillin Binding Protein, PBP1b, in E. coli and provide a molecular mechanism for this function. (1/12).

Draw a ribbon representation of a protein structure shaped like a banana, with alpha-helices, beta-sheets, and loops clearly visible, maintaining realistic molecular geometry and coloring styles typical for protein visualizations.

I think @nytimes.com Spelling Bee needs some Bio101. It also rejects intron, allele (and derivations), and actin. At least it has gene.

What an amazing experience to be at the 76th Mosbacher kolloquim! Awesome talks on protein design and structural biology and a lot of conceptual discussions on where the field is going. Glad to also have been able to present our poster on binder design using BindCraft!

Thank you so much for integrating Foldseek into the great ChimeraX.

🧬 Exciting AlphaFold DB updates: ✅ Bulk downloads – Up to 100 structures (PDB, mmCIF / JSON) ✅ pLDDT filtering – Find high-confidence models ✅ Table exports 📖 Read www.sciencedirect.com/science/arti... 🔗 Explore alphafold.ebi.ac.uk #AlphaFold #AI #Bioinformatics #ProteinStructures

🚀 #AlphaFold Database update AlphaFold DB now integrates The Encyclopedia of Domains (TED) – a resource designed to systematically identify & classify structural domains within AlphaFold-predicted protein structures. www.ebi.ac.uk/about/news/u... @pdbeurope.bsky.social

See your DNA sequences straight in the results email 🤘 Are we the first to do this? Let us know!

Foldseek-Multimer—now published in @naturemethods.bsky.social—our fast multimer search tool, enables complex comparisons against the full PDB in seconds. It comes with BFMD, a collection of 300K+ predictions gathered from community projects. 📄 nature.com/articles/s41... 🌐 search.foldseek.com