I'm really excited to break up the holiday relaxation time with a new preprint that benchmarks AlphaFold3 (AF3)/“co-folding” methods with 2 new stringent performance tests. Thread below - but first some links: A longer take: fraserlab.com/2025/12/29/k... Preprint: www.biorxiv.org/content/10.6...

My uni and many others have tried to centralize and automate many administrative functions. What happens is that the expertise is moved out of the department and then the rest of us suckers are left to learn to become admins and deal with all the edge cases. Such has been the last 6 yrs of my life

Keen to use an open source workflow for nanobody discovery? Check out Alpseq 🦙 Alpseq’s diversity analysis, enrichment counts & clustering allow different approaches for nanobody selection Great collab with bioinformaticians @qgouil.bsky.social Kathleen Zeglinski www.biorxiv.org/content/10.1...

Pigeon fortress

Pomfret Vermont 📸 Ngoc Minh

H.M. Saffer II (American, b.1942) : Moon Waters, 2023 Oil on canvas 30 × 30 in | 76.2 × 76.2 cm Further description & bio in the alt text 👇

‘Protein evolution as a complex system’ – A new Comment discusses protein evolution in terms of complex systems theory and machine learning approaches to model the dynamics of protein evolution www.nature.com/articles/s41...

Thank you everyone for the congratulations and the large number of applications! I want to specifically encourage applications for these positions: * Postdoc in structural biology (cryoEM, ideally with X-ray too) * Full time lab manager/technician with wetlab experience

Protein-ligand complexes are all the rage with OpenBind+other efforts launching 3 amazing papers describing 229 protein-ligand structures just dropped in @actacrystd.iucr.org A tremendous teaching text, but I disagree on the discussed potential for misuse. Read more fraserlab.com/2025/07/29/E...

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!

nothing would make me happier than US science returning to the amazing and transformational legacy of success and dominance but if that's not possible, we need other places with the vision to take over as the pacesetter humanity's long term success demands no less

Pleased to announce I have been promoted to the rank of GRANDMASTER thank you for your attention to this matter

Proud to share our work where we resolved a longstanding question regarding the existence of a human telomerase dimer and provided insights into its function. Led by 3 amazing lab members in collaboration with @yiliangding.bsky.social and @rdaslab.bsky.social. www.science.org/doi/10.1126/...

This paper started probably 20 years ago when I was working with John Oakeshott, a long time in the making and I think a nice summary of a complex real world evolutionary process

Seriously. Pay for review, not publication Publish public reviews Editorial assessment changes until version of record Flexible article types elife-rp.msubmit.net/html/elife-r... Some work todo on reviewer credit (add @prereview.bsky.social to you cv!)

New tools! GreenPy and ApplePy are fluorescent biosensors for pyruvate with huge responses (20–40x in vitro) and a range of affinities (10s of μM to mM). These should be game changers for imaging of metabolism! Great work by Shosei Imai @sikmys.bsky.social and team 👏. www.biorxiv.org/content/10.1...

Average zero-shot mutation effect predictions across related sequences to reduce noise and improve accuracy. @cwjpugh.bsky.social @paulinanunezv.bsky.social @jonnyfrazer.bsky.social Mafalda Dias www.biorxiv.org/content/10.1...

Canberra has excellent sky

We are looking to hire (yes, even in this economy!) a jr. specialist to train in protein prep/structural biology related to our AVOID-ome work as part of openadmet.org. A great position for someone who is looking to be a tech for a few years before grad or med school. aprecruit.ucsf.edu/JPF05424

🚨 preprint 2️⃣ this month: our (purely experimental🧪) venture into #ChemBio We prouldy present: ADD-tagging of proteins (or "ADDing") —a super convenient enzymatic technique to install click chemistry handles on proteins. Led by superstar @wahyuwidodo.bsky.social www.biorxiv.org/content/10.1... A 🧵👇🏽

Are you (or a recent grad or tech/lab manager) looking for an awesome, mission-driven job? Come join us @addgene.bsky.social! Put your lab skills to work making impact for thousands of scientists around the world 💪🧬🧪

Protein Engineering, Design & Selection (PEDS) invites contributions to a Special Collection titled, “Non-Canonical Amino Acids", with guest editors Prof. Huiwang Ai (Virginia) and Prof. Peng Chen (Peking). Send us your best work! academic.oup.com/peds/pages/c...

Some interesting links I'm collecting for folks who want to do advocacy in their local districts. www.ucsf.edu/cgr/advocacy... - easy way to write to your reps! sciencehomecoming.com - write a letter to a hometown newspaper (great for where you grew up or went to undergrad/grad school)

Good autumn in Canberra

Choosing ML architectures for protein engineering is often challenging. Our “new” updated preprint provides a rational framework to match ML models to protein fitness tasks, showing landscape ruggedness influences prediction accuracy. Mahakaran dana Adam et al www.biorxiv.org/content/10.1...

Fractal cabbage

Good read: Inside arXiv - the Most Transformative Platform in All of Science www.wired.com/story/inside...

www.biorxiv.org/content/10.1... why are protein fitness landscapes often very rugged and what does this mean for evolution and engineering? We have been interested in this for a while - in this paper (led by Matt Spence) we look at it quantitatively using eg spectral graph theory.

We unlock breakthrough insights by delivering the best training sets in biology—at unprecedented scale. youtu.be/KuCaJTPHM2o

biorxiv.org/content/10.1... Here’s a paper that was many years in the making. The idea that the climate can affect the thermodynamic mechanism of binding due to the temperature dependence of the entropy term is interesting- we see gradual shift in binding mode along evo trajectory…

Our review on machine learning methods to study sequence–ensemble–function relationships in disordered proteins is now out in COSB authors.elsevier.com/sd/article/S... Led by @sobuelow.bsky.social and Giulio Tesei

‘Travel agencies charge far more than it would cost an academic to arrange their own travel and accommodations - sometimes staggeringly more.’

Isolated in just 3 years! (previously, 12 years). We obtained two strains from 'Hodarchaeales', proposed to be closest to our archaeal ancestor. Our analysis suggests the ancestor was an anaerobic, syntrophic, peptidotrophic, archaeon with a simple intracellular structure and possible aerotolerance.

I am jealous of all my colleagues enjoying Lorne Proteins Meeting and wish I was there, especially since I have a 7 hour curriculum review tomorrow…

It is extremely unfortunate that the statement somehow still made it into the frozen journal version of the paper and in the press releases despite this being pointed out by Brian and others after the preprint was out. It is very nice work but sad to see consistent overhypey statements

FYI the designed esmGFP is 58% identical to the most similar extant GFP sequence - hence "500 million years of evolution" - but nearly half of the novelty (the 42% unaligned part of the seq) is derived from one other protein. Originally caught by @btnaughton.bsky.social, source link in alt text

Check out our work, where we discover how receptor GPCR senses pH! We solved a longstanding question by developing foundational GPCR DMS tech dev + structural bio! Led by brilliant PhD student @matthewkhoward.bsky.social and Nick Hoppe w/ @amanglik.bsky.social! www.cell.com/cell/fulltex...

Many academics point to bioRxiv as “the one thing improving science publishing”. If so, the one thing you all can do is persuade colleagues to submit and make this a norm. 1/2

How do you accelerate rock weathering and mineralization of CO2 without breaking the bank, part 2? Joseph Lee shows how Gluconobacter can be far more effective than organic acids, and drops the amount of sugar carbon to sequester a molecule of CO2 from 525 to 1. www.biorxiv.org/content/10.1...

www.nature.com/articles/s42... Paper on ASR protein ML published (congrats @danasmatthews.bsky.social and everyone else not on Bluesky). Some interesting bits - ASR can generate quality synthetic data, local sequence density important, and evo relationships can yield smoother fitness landscapes

You know an industry is in a bubble ready to burst when real technical critique is derided as being too pessimistic and not having vision. People who are more interested in building something real than hype welcome and learn from criticism

arxiv.org/abs/2412.06115 The emergence of order from disorder, sensitivity to initial conductions, epistasis, the fractal geometry of phylo trees, etc., are all traits protein evolution has in common with other “complex systems”.

Sunset rainbow

This should go chiral

Great new work from former postdoc @dkeedy.bsky.social 's lab at CCNY! And continuing his trend of amazing titles!

We have new postdoc positions available. Please apply if you are interested in protein engineering, continuous evolution, OrthoRep, and/or synthetic biology! recruit.ap.uci.edu/JPF09324. Some particular problems we have a unique angle of attack on include…

dealing with the ruggedness of protein fitness landscapes is perhaps the most challenging aspect of protein design and engineering - here we have written a short perspective about it - it's complicated and not perfectly understood but very interesting! arxiv.org/abs/2411.12957