Arriën Symon Rauh

We (@sobuelow.bsky.social) developed AF-CALVADOS to integrate AlphaFold and CALVADOS to simulate flexible multidomain proteins at scale

See preprint for:
— Ensembles of >12000 full-length human proteins
— Analysis of IDRs in >1500 TFs

📜 doi.org/10.1101/2025...
💾 github.com/KULL-Centre/...

Excited to see our review now on arXiv, written together with @fpesce.bsky.social and @lindorfflarsen.bsky.social

doi.org/10.48550/arX...

New preprint is out !

Bad news : current all-atom simulations of phosphorylated IDPs are very probably wrong (and yes, this is clickbaity on purpose 😇)

Good news : we know what to blame for it, and we even have an idea of how to fix it !

Our paper on:

A coarse-grained model for simulations of phosphorylated disordered proteins

(aka parameters for phospho-serine and -threonine for CALVADOS)

is now published in Biophysical Journal

authors.elsevier.com/a/1lTcE1SPTB...

@asrauh.bsky.social @giuliotesei.bsky.social & Gustav Hedemark

Arriën & Giulio's paper on

A coarse-grained model for disordered proteins under crowded conditions

(that is the CALVADOS PEG model) is now published in final form:
dx.doi.org/10.1002/pro....

@asrauh.bsky.social @giuliotesei.bsky.social

AlphaFold is amazing but gives you static structures 🧊

In a fantastic teamwork, @mcagiada.bsky.social and @emilthomasen.bsky.social developed AF2χ to generate conformational ensembles representing side-chain dynamics using AF2 💃

Code: github.com/KULL-Centre/...
Colab: github.com/matteo-cagia...

Led by @sobuelow.bsky.social & @giuliotesei.bsky.social we put together a full overview of the CALVADOS software and applications.

Give it a read: doi.org/10.48550/arX...
Give it a try: github.com/KULL-Centre/...

Thanks to @lindorfflarsen.bsky.social and all authors for this wonderful project on predicting IDR phase separation from sequence!

Check out the published version (including added exp. data from @tanjamittag.bsky.social) and feel free to try out our webserver.

Very happy to share our next extension to the CALVADOS protein force field:

If you want to explore the changes in global dimensions of a disordered protein upon phosphorylation: give it a read and a try!

Big thank you to @giuliotesei.bsky.social, @lindorfflarsen.bsky.social and Gustav S. Hedemark

A coarse-grained model for disordered proteins under crowded conditions

Big thank you to Giulio Tesei and @lindorfflarsen.bsky.social for their guidance.

The preprint can be found here: www.biorxiv.org/content/10.1...

The code and data are available here: github.com/KULL-Centre/...

Excited to share our PEG model for disordered proteins in CALVADOS!

If you are interested in exploring the effects of a crowder on the global dimensions of an IDP or want to explore the phase separation behaviour of a more weakly PS-prone IDP, have a look at our preprint and give it a try.

Figure from manuscript showing epresentative snapshots from slab simulations with 100 chains A1 (dark blue) with w/v-percentages of 0%, 5% (100:127) and 10% (100:254) PEG8000 (orange chains, 181 monomers) illustrating how PEG both lowers the 𝐶sat with increasing concentrations and also increases the effective protein concentration in the condensate (𝐶con).

Preprint submitted 🇺🇦

Molecular grammars of intrinsically disordered regions that span the human proteome Intrinsically disordered regions (IDRs) of proteins are defined by functionally relevant molecular grammars. This refers to IDR-specific non-random amino acid compositions and non-random patterning of...

www.biorxiv.org/content/10.1...

Figure from the paper that illustrates the approach of probing the transition state for amyloid growth by experiments and simulations

How do proteins mis-fold?

Paper led by Jacob Aunstrup from Alex Büll’s lab with MD simulations by Abigail Barclay, and key contributions from several others. We combined measurements of Φ-values with MD simulations to study the transition state for amyloid fibril growth

doi.org/10.1038/s415...

Check out @rasmusnorrild.bsky.social's work with Alex Buell and Joe Rogers developing and using Condensate Partitioning by mRNA-Display to probe phase separation of ~100.000 sequences, and @sobuelow.bsky.social's simulations to support and analyse the experiments
www.biorxiv.org/content/10.1...

Systematic characterization of indel variants using a yeast-based protein folding sensor Larsen-Ledet et al. developed a yeast-based protein folding sensor to determine the effects of indel variants in DHFR. Using a saturated indel library, it was found that most indels are not tolerated. Several are temperature sensitive and folding is rescued by methotrexate. Rosetta and AlphaFold2 predictions correlate with the observed effects.

In our new paper we characterize the effects of indel variants on protein folding and stability using a new yeast-based protein folding sensor. The work was led by Sven Larsen-Ledet and supported by the @novo-nordisk.bsky.social.
Link to paper: www.cell.com/structure/fu...

Meet the CALVADOS RNA model

Ikki Yasuda, Sören von Bülow & Giulio Tesei have parameterized a simple model for disordered RNA. Despite it's simplicity (no sequence, no base pairing) we find that it captures several phenomena that depend on the charge, stickiness and polymer properties of RNA 🧬🧶🧪

Flyer for the course Keeping up with the interactome - How IDPs work including a list of speakers: Professor Tanja Mittag, St Jude Children’s Hospital, Memphis, US Professor Kresten Lindorff-Larsen, BIO, SCIENCE, UCPH Professor Ylva Ivarsson, Uppsala University, Sweden Dr. Michael Wehr, Systasy Bioscience, Munich, Germany Professor Zsuzsanna Dostztányi, Eötvös Loránd University, Hungary Professor Kristian Strømgaard, HEALTH, UCPH Professor Stefano Gianni, Sprienza University of Rome, Italy Professor Per Jemth, Uppsala University, Sweden Dr. Franziska Schöppe, Novo Nordisk A/S, Denmark Professor Benjamin Schuler, University of Zurich, Switzerland Professor Alfonse De Simone, University of Naples, Italy Dr. Malene Ringkjøbing Jensen, CNRS, Grenoble, France Alleyn Plowright, Chief Scientific Officer, Pangea Bio, London UK Professor Birthe B. Kragelund, BIO, SCIENCE, UCPH

If you are a PhD student and like protein disorder (or want to learn more), Birthe Kragelund @bbkrage.bsky.social and Kristian Strømgaard are organizing a PhD course on How IDPs work 🧶🧬🧪 Note the cost if you are not at a Danish university.

Details: phdcourses.ku.dk/DetailKursus...

Identifying Sequence Effects on Chain Dimensions of Disordered Proteins by Integrating Experiments and Simulations It has become increasingly evident that the conformational distributions of intrinsically disordered proteins or regions are strongly dependent on their amino acid compositions and sequence. To facili...

New collaborative work in collaboration with the labs of Robert Best & Tanja Mittag driven by Ben Schuler.
Identifying Sequence Effects on Chain Dimensions of Disordered Proteins by Integrating Experiments and Simulations.
pubs.acs.org/doi/10.1021/...