Tina Perica

Reading that text I was convinced that this lady is indeed no intellect, just emotions. No facts or math, just gossip. And then she just concluded all women must be like that.

May her memory be a blessing.

The amount of AI generated art in slides at this conference, primarily used by older scientists, is killing me. Scientists please. Don’t use these ai platforms to make your figures or slides. They look bad and I have yet to see them meaningfully improve the message of talks.

Oh, bloody brilliant! Guess what I’m replying next time I don’t care to review something!

Nice work. Thanks for a fantastic skeetorial, always appreciated

The @nytimes.com decided last year what the story was; Trump II was the righteous punishment visited upon their interns and junior staffers and grandchildren for being so annoying about MeToo and BLM, and once they understood that and repented, they could have democracy back.

I wrote a blog post about the future of structural bioinformatics.

Where to go after AlphaFold? How do we avoid the field becoming a load of half-baked LLMs?

Let me know what you think.

jgreener64.github.io/posts/struct...

I’ll let you know if we see anything interesting!

One thing is for sure, fun with RAF never ends! (10/10)

One thing took us by surprise: It seems that the asymmetric dimer comes at the end of the RAF activation cycle. We got more structures and saw that the Receiver looks the most like a canonical active kinase. Is the asymmetric conformation then the final catalytically active state of RAF? (9/10)

If we titrate those mutants into cells with wild type RAFs in the background, we should see a dose dependent effect. And we did. The beautiful model must be correct! (8/10)

But what is the difference between active asymmetric and active symmetric structures? We made BRAF mutants
(i) AAAA mutant = Receiver but not Activator
(ii) Kinase-dead mutant = Activator but not Receiver
(iii) Double mutant = neither
(7/10)

This work started by Yasushi Kondo solving an X-ray crystal structure of BRAF in complex with its substrate MEK1 where the BRAF dimeric interface was asymmetric, with the NtA motif of only one of the subunits making interface contacts. Yes, like in that beautiful model! (6/10)

However, to paraphrase the late Cyrus Chothia, if the data don't fit a beautiful model, you need more data. You can't just forget about the NtA - cancer genetics and the early Marais experiments don't allow it! (5/10)

The problem? Multiple BRAF and CRAF structures were solved since, and … dimers were symmetric, kinases looked active, and the NtA looked disordered. (4/10)

Allosteric Activation of Functionally Asymmetric RAF Kinase Dimers Although RAF kinases are critical for controlling cell growth, their mechanism of activation is incompletely understood. Recently, dimerization was sh…

15 years later, Susan Taylor et al proposed a model: Active RAFs are dimers and one subunit (the "Activator") uses its NtA to activate the other subunit (the "Receiver"). It is only the Receiver that takes the fully active kinase conformation. tinyurl.com/RAFmodel (3/10)

Serine and tyrosine phosphorylations cooperate in Raf‐1, but not B‐Raf activation | The EMBO Journal EMBO Press is an editorially independent publishing platform for the development of EMBO scientific publications.

In 1999, Marais lab showed that this is because of the 4-residue N-terminal acidic (NtA) motif. In CRAF, the NtA must be phosphorylated to become acidic and the kinase to become active. In BRAF the NtA is already acidic, making BRAF one step closer to (over)active. tinyurl.com/NtAmotif (2/10)

Mechanism of MEK1 phosphorylation by the N-terminal acidic motif-mediated asymmetric BRAF dimer The RAF/MEK/ERK signaling cascade regulates cell proliferation and differentiation and is frequently dysregulated in cancer. Approximately 90% of RAF-mutant cancers harbour mutations in B-type of Rapi...

Skeetorial on our BRAF preprint!
tinyurl.com/asymmBRAF
The RAS->RAF->MEK->ERK cascade carries mutations in most human cancers. Interestingly, although we have three RAF paralogues (A, B and C), it is the BRAF that is predominantly mutated in cancer patients. (1/10)

For every Nobel that goes to a criminally under-recognized woman scientist (Brunkow, Karikó), or fails to go (Candy Lee), a week of mourning and reform for an academic system wherein you can do Nobel-prize-worthy-work and still end up without a conceivable path to being a professor.

It’s the chicken or the egg question. We are only now realising this layer is important because it was so hard to study. And because of that, people studying it probably didn’t do well in their careers

Seems like they also listen to Ghost at Science!

😅

First work on kinases from my lab! Working on this project, I often remembered the late Cyrus Chothia who said that if the data doesn’t fit a beautiful model, maybe it’s not the model, maybe you just need more data. :)

How Can We Live Together? - Boston Review Ezra Klein is wrong: shame is essential.

In case you missed it: an essential piece from Olúfẹ́mi O. Táíwò from earlier this week:

www.bostonreview.net/articles/how...

Mechanism of MEK1 phosphorylation by the N-terminal acidic motif mediated asymmetric BRAF dimer https://www.biorxiv.org/content/10.1101/2025.09.26.678760v1

Slightly diminish a book

Windy Heights

A global genetic interaction map of a human cell reveals conserved principles of genetic networks We generated a genome-scale, genetic interaction network from the analysis of more than 4 million double mutants in the haploid human cell line, HAP1. The network maps ∼90,000 genetic interactions, in...

Monumental effort from @maxbillmann.bsky.social and colleagues, quantifying genetic interactions among 4 million human gene pairs. Lots of features associated with genetic interaction & GI degree conserved from yeast. www.biorxiv.org/content/10.1...

I also really dislike that talking about AI in this way by journalists - and discrediting humans who actually worked on a paper in the process - is basically free advertising for the AI industry.

AI designs new superbug-killing antibiotics for gonorrhoea and MRSA Two new potential drugs have been designed by AI to kill drug-resistant bacteria, in a major Massachusetts Institute of Technology study.

ECRs who probably did the bulk of the work go completely unmentioned in the piece, in lieu of putting all credit on some anonymous and benevolent AI force that's probably just a few tens of millions of weights in a PyTorch model

Article on BBC news. Title: AI designs antibiotics for gonorrhoea and MRSA superbugs Description: Two new potential drugs have been designed by AI to kill drug-resistant bacteria, in a major Massachusetts Institute of Technology study.

I really dislike how science has started calling almost any fancy computational technique AI. 🧪

The framing of this entire article makes it sound like a benevolent AI independently made these drugs.

That is *pure fantasy*.

Instead: a team of scientists made a machine learning model for a study.