Kresten Lindorff-Larsen

The Division of Biological Physics @mpipks.bsky.social seeks a Research Group Leader in #biophysics, #softmatter physics, or related areas. (Further particulars in the ad.)

Apply by the 3rd of April 2026 at pks.mpg.de/bprgl to join us in Dresden!

Cupriavidus necator, an alternative source for isotopic enrichment of proteins expressed in insect cells for NMR investigations - Journal of Biomolecular NMR Isotopic enrichment of pharmacologically relevant protein targets is crucial for structural studies by nuclear magnetic resonance (NMR) and plays a key role in advancing structure-guided drug discover...

Have a look at our latest publication:
Cupriavidus necator as an alternative source for 15N/13C isotopic enrichment of proteins expressed in insect cells for NMR - enabling structural studies of disease-relevant targets.

Full text link:
link.springer.com/article/10.1...

a little girl is asking why not both while standing in a kitchen . ALT: a little girl is asking why not both while standing in a kitchen .

On the todo list

10712 cups/12 years ~ 2.5 cups/day

Coffee and Tea Intake, Dementia Risk, and Cognitive Function
doi.org/10.1001/jama...

My trusted Jura has made myriad coffee and needed some TLC. Look forward to having it back

First preprint of the @pollyfordyce.bsky.social and @dunnlab.bsky.social collaboration! We used high-throughput microfluidics for sequence-strength mapping at the single-molecule level. Our new tech allowed us to discover a fundamental nonequilibrium property of multivalent systems. 1/13

Silvia's simulations showed that while all epitopes expose Sia for binding, Siglec-6 recognises and binds only GM1 because of a key interaction with the membrane through W127 and K126, which orientates the V-set domain to bind the Sia through Arg122 and the terminal Gal to the C-C' loop 😎

Maddipatla, Rzayev, Pegoraro, Pacesa, Schanda, Marx, Vedula, Bronstein: Inference-time optimization for experiment-grounded protein ensemble generation https://arxiv.org/abs/2602.24007 https://arxiv.org/pdf/2602.24007 https://arxiv.org/html/2602.24007

The Dynamic Lives of Intrinsically Disordered Proteins Shapeshifting proteins challenge a long-standing maxim in biology.

Very nice article by Danielle Gerhard in The Scientist on

“The Dynamic Lives of Intrinsically Disordered Proteins”

with quotes from Gabi Heller, @alexholehouse.bsky.social and myself about our shared love of and fascination with these proteins

www.the-scientist.com/the-dynamic-...

RNA: simple alphabet, complex grammar
— Sandro Bottaro, 2017

The most consistent thing I have learnt about RNA is that my intuition based on proteins tends to fail when applied to RNA

President Ribbon

Whoo hoo!! What an honor and a pleasure to add a new ribbon at the #BPS2026 this morning!
@biophysicalsoc.bsky.social

Yeah, it would perhaps have been better; I don’t think we ever got around to implementing it as the rotamer library background is only a small part of the prior that we use

I think we have some evidence that using AF3 helps a bit.

In this case it's not about predicting a single rotamer per structure, but actually to get the dihedral angle distributions sampled at equilibrium
bsky.app/profile/lind...

Looking forward to present our work on predicting protein side-chain rotamer distributions with AlphaFold2 Monday 8:30 at #bps0226

But you should also consider instead going to the The Future of Biophysics Symposium at 9:15 to hear Giulio Tesei talk about his work on data-driven modelling of IDPs

Very interesting

Would be good to adopt these method for other E3s

Happy to share our newest preprint on Parkin missense variants in work led by Erna Sol &
@vvouts.bsky.social in @rhp-lab.bsky.social

Using a multiplexed assay we determined the effects of 9,212 out of 9,300 single amino acid substitutions and nonsense Parkin variants. 1/n

doi.org/10.64898/202...

The fitness landscapes of binders targeting protein surfaces that are evolutionarily predisposed to engage in PPIs is much narrower and deeper than those that target surfaces with no known interacting proteins. This might be b/c random binding events is bad, and selected against

The campus at @au.dk is very pretty, also in the snow

This provides a unique opportunity to test the robustness of multiplexed assays of variant effects. The 2 maps were generated in different labs & cell lines, with different libraries and readouts of Parkin function (mitophagy vs phospho-ubq). The maps correlate and equally predict pathogenicity! 4/4

But, wait, there's more...

As we were finishing our work we learnt that Greg Kudla and colleagues were performing independent work on a map of Parkin function and abundance using a complementary approach.

So we contacted them & delayed submission to coordinate our preprints. 3/n

We combine our new functional map with our previously generated VAMP-seq map of protein abundance to interpret mechanisms for Parkin loss (and gain) of function, and show how the map can be used to distinguish pathogenic and benign variants. 2/n

Happy to share our newest preprint on Parkin missense variants in work led by Erna Sol &
@vvouts.bsky.social in @rhp-lab.bsky.social

Using a multiplexed assay we determined the effects of 9,212 out of 9,300 single amino acid substitutions and nonsense Parkin variants. 1/n

doi.org/10.64898/202...

Congrats Alex. A classic already before it got published

Picture of one of the lakes in central Copenhagen

Image of the Danish newspaper Politiken with an article discussing the planned "Søringen" highway

Conversely, there was an attempt in the 50s–60s to construct a new 10–12 lane highway next to the lakes in central Copenhagen. Fortunately, those plans were shelved

danishdesignreview.com/townscape/20...

da-wikipedia-org.translate.goog/wiki/S%C3%B8...

Roses are red
Violets are blue
If you fall in love with your hypothesis
You’ll be biased to prove it true
🧪

tomato

STI1 domain engages transient helices to mediate Dsk2 phase separation and proteasome condensation - The EMBO Journal Ubiquitin-binding shuttle proteins are important components of stress-induced biomolecular condensates in cells. Yeast Dsk2 scaffolds proteasome-containing condensates via multivalent interactions wit...

Yeast ubiquilin Dsk2 scaffolds proteasome-containing condensates under stress via multivalent interactions – @castanedalab.bsky.social et al show how dynamic interactions among its STI1 domain & transient helices in its disordered region promote its phase-separation
link.springer.com/article/10.1...

On this International Day of Women and Girls in Science I (as in previous years) take an Implicit Association Test to remind myself of my potential biases and with the goal of remembering to take them into account

You too can do this at:
implicit.harvard.edu/implicit/

And a new paper from the lab. A follow up to a previous study in which we elucidate the mechanism of the nuclear transport. Read the full story: www.nature.com/articles/s41...