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!

Kempner Institute at Harvard University@kempnerinstitute.bsky.social · 6d ago

Announcing the newest #KempnerInstitute Accelerator Award recipients! Congratulations to Maha Farhat, Wade Harper (@harperlabhms.bsky.social) & Edward Huttlin (@edhuttlin.bsky.social), Noor Youssef & Debora Marks (@deboramarks.bsky.social), and Samuel Kou. 🎊 Learn more ➡️ bit.ly/4wyuaxx

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/...

A broadly conserved gram-positive lipoprotein regulates cell elongation | PNAS

The cell wall peptidoglycan (PG) protects virtually all bacteria from osmotic lysis and specifies cell shape. Synthesis of this exoskeleton is carr...

pnas.org

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👇

Structural motif search across the protein universe with Folddisco - Nature Biotechnology

Folddisco enables protein structural motif search in million scale databases.

nature.com

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.

bioRxiv Microbiology@biorxiv-microbiol.bsky.social · 3mo ago

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

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)

Evaluating generalization in protein–ligand cofolding methods - Nature Structural & Molecular Biology

This work introduces the Runs N’ Poses dataset for benchmarking deep learning methods on the protein–ligand complex prediction task. It shows that current methods rely on memorization, challenging the...

doi.org

Peter Škrinjar@peterskrinjar.bsky.social · last yr.

Excited to share our latest preprint evaluating AlphaFold3, Boltz-1, Chai-1 and Protenix for predicting protein-ligand interactions, featuring our newly introduced benchmark dataset 🌹Runs N’ Poses🌹! www.biorxiv.org/content/10.1... 🧵👇 (1/n)

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/...

Identification of sporulation genes in Bacillus anthracis highlights similarities and significant differences with Bacillus subtilis

How good is Bacillus subtilis as a model for the spore-forming pathogen Bacillus anthracis? Using high throughput genetics to identify B. anthracis sporulation genes and cytological analysis of the mu...

journals.plos.org

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/...

Rapid compensatory evolution within a multiprotein complex preserves telomere integrity

Intragenomic conflict with selfish genetic elements spurs adaptive changes in subunits of essential multiprotein complexes. Whether and how these adaptive changes disrupt interactions within such comp...

science.org

Online now: A metabolic atlas of mouse aging

A metabolic atlas of mouse aging

Pilley et al. describe how metabolite levels change in 12 organs from male and female mice across five ages, spanning adolescence to old age. They reveal that organs show distinct age- and sex-specific changes in metabolism. They also develop metabolic clocks that predict putative metabolic drivers of aging, including hydroxyproline.

dlvr.it

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

Thrilled to share that the final piece of my PhD work is now on bioRxiv! biorxiv.org/content/10.1... With support from @nvidia and the @NSF, we used AlphaFold to screen 1.6M+ protein pairs, revealing thousands of potential novel PPIs. All data can be viewed at predictomes.org/hp

Proteome-wide in silico screening for human protein-protein interactions

Protein-protein interactions (PPIs) drive virtually all biological processes, yet most PPIs have not been identified and even more remain structurally unresolved. We developed a two-step computational...

biorxiv.org

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...

Structure Prediction and Design using AlphaFold – Sami Chaaban

YouTube video by MRC Laboratory of Molecular Biology

youtube.com

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/

Predictomes | AF3 ANALYSIS

A free interactive resource for viewing predicted AlphaFold multimer structures for protein pairs in biological pathways.

predictomes.org

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...

Cyclic-di-AMP modulates cellular turgor in response to defects in bacterial cell wall synthesis - Nature Microbiology

Brogan et al. uncover a signalling pathway in which levels of the nucleotide second messenger c-di-AMP increase in response to defects in cell wall synthesis. This regulatory pathway decreases turgor ...

nature.com

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...

EndoMAP.v1 charts the structural landscape of human early endosome complexes - Nature

A study presents EndoMAP.v1, a resource that combines information on protein interactions and crosslink-supported structural predictions to map the interaction landscape of early endosomes.

nature.com

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

What Happens When a Gene Quality-Control Mechanism Fails?

Study solves riddle of how mutations in Integrator complex relate to neurodegeneration, cancer

tinyurl.com

 🧬🎉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... 🧵🧪

Zero-shot design of drug-binding proteins via neural selection-expansion

Computational design of molecular recognition remains challenging despite advances in deep learning. The design of proteins that bind to small molecules has been particularly difficult because it requ...

biorxiv.org