Amazing paper. A megadalton enzyme complex that: - combines both electron bifurcation AND confurcation steps - has a new type of iron-sulfur cluster - a new kind of weird electron transfer path - super charges electrons to reduce aromatic rings - also powers respiration 😳

1/ Excited to share our preprint! 🥳 Degradation of aromatic compounds, including BTEX pollutants, requires highly endergonic aromatic ring reduction. Using #cryoEM and in situ #cryoET, we show how BCRII couples electron bifurcation modules in one giant redox machine www.biorxiv.org/content/10.6...

One of biggest mysteries in biology: how did complex eukaryotic cells evolve from simple microbes? ~1.8 billion years ago, an archaeal cell likely merged with a bacterium to form the first eukaryotic cell, but can we ever find direct evidence of this transformative event? 🦠 🚶‍♂️

Really excited that this major work from my PhD is finally published in @plosbiology.org ! In it, we were trying to tackle a fundamental question in evolution - how do genetic mutations map onto evolutionary fitness? (1/n) journals.plos.org/plosbiology/...

Found out today that @kyclark.bsky.social has made their great 'Mastering Python for Bioinformatics' book into a YouTube series. youtube.com/playlist?lis...

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

This has been up for a while but I haven’t really publicized it. Introducing ciMIST: sparse, self-consistent network models of local and global protein conformational entropy, learned from molecular dynamics. This helps with analyzing MD and connecting to experiments www.biorxiv.org/content/10.1...

Having a hard time keeping up with the fast-moving field of origin of eukaryotes/Asgards archaea? Our new perspective article can help, we review the status of research over the last decade and where it's going. The archaeal roots of eukaryotic life www.pnas.org/doi/10.1073/...

New OpenFold3 preview out! (OF3p2) It closes the gap to AlphaFold3 for most modalities. Most critically, we're releasing everything, including training sets & configs, making OF3p2 the only current AF3-based model that is functionally trainable & reproducible from scratch🧵1/9

New paper showing that much of the apparent success of protein language models in predicting mutational effects is a mirage: These models mostly memorize sites. 1/ www.biorxiv.org/content/10.6...

“Some have even argued that private funding is superior, maintaining that it is more flexible, less prone to groupthink, and reduces the “burden” on taxpayers. But can the private sector really replace public funding? History suggests not” www.science.org/doi/10.1126/...

A minimal PyTorch re-implementation of AlphaFold2 github.com/ChrisHayduk/... We need more stuff like this. The incentive is to always be making the new groundbreaking tool, while maintenance + improvement of "old" tools gets left behind. But there is still heaps to be gained in "old" tools

Aerobic syngas conversion: opportunities, challenges, and solutions www.sciencedirect.com/science/arti...

Any paper that quotes Italo Calvino is an instant 10/10 in my book 'An Interpretation, Survey, and Outlook of Microbial Macroecology' by @shoestrapped.bsky.social ecoevorxiv.org/repository/v...

Insects were my first scientific love (before I knew about proteins). So I love hearing about some new weird insect "Temnothorax kinomurai is the first ant species known to lack both workers and males and to consist exclusively of queens" doi.org/10.1016/j.cu... @currentbiology.bsky.social

Understanding how enzymes work: the journey to ensemble–function studies febs.onlinelibrary.wiley.com/doi/10.1111/... This is an exceptionally well written review on how enzymes work. Rather than the structure-function relationship, Herschlag & Du analyse the ensemble-function relationship

Structural ontogeny of protein-protein interactions: www.science.org/doi/10.1126/... Fundamental work on how PPIs (co)evolve, combining directed evolution and machine learning to reveal the role of chance and contingency.

Can we simulate realistic evolutionary trajectories and “replay the tape of life”? In this work, we propose a flexible, generalizable deep learning framework for modeling how the entire protein sequence evolves over time while capturing complex interactions across sites. 1/n doi.org/10.64898/202...

You go, Katy! 🚀 I’m so proud of you, and so happy to finally see this in its final form! Count me in on your corner to keep on cheering for you! Looking forward to doing more amazing science together 💪 Check @katyappler.bsky.social thread below for highlights and the full paper here: rdcu.be/e4A70

Asgard archaeal origin of microtubules: www.biorxiv.org/content/10.6...

I present this extremely niche meme for the hydrogenase community

"GenAI increases output and helps programmers expand into new domains—but only for senior- level developers. Early-career developers, despite being the most enthusiastic adopters, see no measurable gains" www.science.org/doi/10.1126/...

Our work is published today: ‘Oxygen metabolism in descendants of the archaeal-eukaryotic ancestor’. This was a huge effort lead by @katyappler.bsky.social. Extremely grateful to have been a part of this amazing project! 😊🦠🧬 Links: www.nature.com/articles/s41... www.nature.com/articles/s41...

Finally out in @nature.com: a new piece of the puzzle of how complex life evolved. Lead by @archaeal.bsky.social & @katyappler.bsky.social. Great collab with @greening.bsky.social and @kassipan.bsky.social. More pieces to follow soon! www.nature.com/articles/s41...

One of the biggest questions in biology is how complex cells evolved about 2 billion years ago. Here's my new story on how scientists are solving the mystery of eukaryotes like us. Gift link: nyti.ms/4qMbo22

At long last! Check out the link to our publication in @nature.com to learn more. doi.org/10.1038/s415... 12/12

New paper from my team detailing a greatly expanded genomic database of Asgard archaea revealing of high energy metabolism those related to eukaryotes! Led by @katyappler.bsky.social lots of help from @jameslingford.bsky.social @valdeanda.bsky.social @kassipan.bsky.social doi.org/10.1038/s415...

Keep hearing hype around vibe coding and how its going to replace all coding very soon. So I look into pro-vibe coding communities on reddit. They all say you have to hold the hand of the AI at every step of the way and have very long but specific prompts, otherwise the AI makes a mess... 1/2

I’ve officially started my lab at Monash University! 🎉 We’re diving into #cellgrowth and #lysosome biology, through the lens of molecular #structure and mechanism. I’m thrilled to say that PhD student scholarships are available—so please share widely and get in touch if you’re interested. 🤩

Passioned by #bioenergetics? Do not miss our new article on the evolutionary history of oxidoreductases with G. Borrel and @sgribaldo.bsky.social @archaeal.bsky.social @valdeanda.bsky.social @pasteur.fr @cnrs.fr @cnrsbiologie.bsky.social @natecoevo.nature.com (www.nature.com/articles/s41...).

'The perpetual motion machine of AI-generated data and the distraction of ChatGPT as a "scientist"' (2024) www.nature.com/articles/s41... An important read providing some sanity against the current AI hype slop that I've been inundated with these past couple of weeks

Goodbye Lorne Proteins 2026. An inspiring few days seeing the best of protein science. @lorneproteins.bsky.social

The Elsevier investigation mentioned was initiated after a STAT news piece on the problem, co-authored with Cathryn, @dsamorod.bsky.social, @stairwaytokevin.bsky.social, @jedidiahcarlson.com, @jameslingford.bsky.social and @jowiph.bsky.social www.statnews.com/2024/06/20/r...

Super cool talk from @kmichie.bsky.social. Lots of examples of how AlphaFold3 does weird stuff

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!

As much as I like making plots with matplotlib and seaborn, the way repositioning legends/colourbars works is super unintuitive and a massive timesink.

Viro3D paper is out! We predicted 85,000 protein structures from human & animal viruses. 1/5 🧵 📑 Paper doi.org/10.1038/s443... 🔭 Explore virosphere viro3d.cvr.gla.ac.uk

RFdiffusion3 is here: www.biorxiv.org/content/10.1...

Switched from using pandas to @pola.rs and it has been a total life saver. Handling dataframes is way more intuitive with the method chaining syntax. Prettier terminal printing, better error messages, lightning fast, fewer headaches.

Recent advances in the inference of deep viral evolutionary history journals.asm.org/doi/10.1128/... A review on structural phylogenetics utility and limitations

Fantastic review on methodological developments in protein structural phylogenetics academic.oup.com/gbe/article/...

Large protein databases reveal structural complementarity and functional locality www.nature.com/articles/s41...

RFdiffusion2 is now live! github.com/RosettaCommo... You can now design proteins, and in particular enzymes from just partially defined amino acid side chains, and without defining their sequence position or order!

This is a remarkable paper on protein evolution from the Lehner lab. What makes it especially cool is that all the code to reproduce all the analysis/plots is included in Jupyter notebooks up on Github www.science.org/doi/10.1126/... github.com/lehner-lab/c...

Just to piggyback on this critique of LLMs for coding with some of my own critiques: • it's a bad idea to install a tool on your machine that has vast read+write permissions • code that works but is really outputting false info is a real danger and hard to catch. LLMs make that danger worse

Does sequence clustering confound AlphaFold2? www.sciencedirect.com/science/arti... From @hkws.bsky.social

MMseqs2 v18 is out - SIMD FW/BW alignment (preprint soon!) - Sub. Mat. λ calculator by Eric Dawson - Faster ARM SW by Alexander Nesterovskiy - MSA-Pairformer’s proximity-based pairing for multimer prediction (www.biorxiv.org/content/10.1...; avail. in ColabFold API) 💾 github.com/soedinglab/M... & 🐍

Pretty amazing looking tool for analysing genetic neighbourhoods: github.com/chevrettelab...

💥 Excited to introduce Bacformer 🦠 - the first foundation model for bacterial genomics. Bacformer represents genomes as sequences of ordered proteins, learning the “grammar” of how genes are arranged, interact and evolve. Preprint 📝: biorxiv.org/content/10.1... 🧵 1/n

Excited to share our work on WitChi! 🛠️🖥️ We tested it on the GTDB r220 archaeal supermatrix (5,869 taxa & 10,101 cols) removing 55% of sites in <2h. The phylogeny showed several interesting groupings with overall improved branch support: #phylogenetics #ArchaeaSky #MSA #opensource #MEvoSky #MicroSky