We can design "static" binders routinely now, but design of "dynamic" shape-changing proteins has remained quite hard. Jeffrey Chang and I asked: why can't we couple small-molecule binding to shape change? After all, natural proteins do it every day. In a new preprint, we show how it can be done. 🧵

Kinase-specific phosphorylation of tau outside the amyloid core encodes fibril fold selection https://www.biorxiv.org/content/10.64898/2026.08.04.742669v1

Light Martini water accelerates sampling in coarse-grained molecular dynamics simulations https://www.biorxiv.org/content/10.64898/2026.08.03.741232v1

Why do intrinsically disordered proteins behave so weirdly during SDS-PAGE? This is the question we aim to answer in our recent paper: onlinelibrary.wiley.com/doi/10.1002/...

Sequence determinants of the hypomobility of intrinsically disordered proteins in <fc>SDS</fc>‐<fc>PAGE</fc>

Proteins with intrinsically disordered regions (IDRs) migrate at a higher apparent molecular weight in sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, complicating their analysis and...

onlinelibrary.wiley.com

Compositional control of FUS condensate ageing through aggregation-prone interaction networks https://www.biorxiv.org/content/10.64898/2026.07.31.741205v1

Chen, Kam, Li, Medina-Ortiz, Damour, Chabriat, Miranville, Bessafi, Cadet: Quaternionic Response Geometry for Proteins: Toward a Noncommutative Theory of Ordered Deformations https://arxiv.org/abs/2607.29101 https://arxiv.org/pdf/2607.29101 https://arxiv.org/html/2607.29101

Competing Molecular Interactions Govern the Dynamical Arrest of G3BP1 Condensates https://www.biorxiv.org/content/10.64898/2026.07.31.741769v1

New @talusbio.bsky.social #AI preprint just dropped 🚀 Meet Ptarmigan-1. It predicts which small molecules bind a protein, and which residues they hit, from sequence and 2D chemistry alone. No structures, no docking, no poses. www.biorxiv.org/content/10.6... Time for a 🧵 (1/13)

Structure-free, site-resolved contrastive learning extends small-molecule discovery beyond the reach of structure-based modeling

Virtual screening asks which molecules, among an enormous space of drug-like chemistry, are worth synthesizing and testing against a protein target. Most modern methods answer by building and scoring ...

biorxiv.org

Happy to share my new paper from the @nogaleslab.bsky.social, combining #cryoEM and #cryoET to solve how Kinesin-4 KIF21B tail binds to microtubules! Our work shows how the specialized tails of KIF21 kinesins allow both #microtubule attachment and crosslinking. www.biorxiv.org/content/10.6...

(Part 1/2) Excited to share our recent work with contributions from Dr. Busra Ozguney and Dr. Priyesh Mohanty, in collaboration with Prof. Nicolas Lux Fawzi’s group (@nicolasluxfawzi.bsky.social) at Brown University, now published in PNAS (doi.org/10.1073/pnas...)!

Fold-switching proteins carry the information required to change their conformations in the unfolded state itself, the MD simulation study finds.

Signatures of protein fold switching in the unfolded state

We have recently shown that, in simulations of unfolded globular proteins, the native contacts are distinguished by their mutual cooperativity, such that this can be used to identify native contact…

cell.com

Excited to see our recent work on the structural mechanism of α/β-tubulin biogenesis featured on the #CryoSPARC blog! 🎉 Many thanks to the team at @structurabio.bsky.social Biotechnology for highlighting both the study and the #cryo-EM workflow that made these structures possible. Read more here:

Structura Biotechnology@structurabio.bsky.social · 6d ago

🔬 Cryo-EM Reveals the Molecular Machinery of Tubulin Assembly In a recent study from @ucdavis.bsky.social, #cryoEM and #CryoSPARC were used to uncover the molecular mechanism underlying α/β-tubulin biogenesis! Read more on the latest CyoSPARC blog 👉 cryosparc.com/blog/tubulin

Integrative Ensemble Modeling reveals RNA conformations targetable by small molecules https://www.biorxiv.org/content/10.64898/2026.07.28.741152v1

How a highly acidic SH3 domain binds to its intrinsically disordered partner through the formation of an encounter complex intermediate https://www.biorxiv.org/content/10.64898/2026.07.28.741257v1

Huge congrats to the many authors who over MANY years worked on this (but especially @karaehunt.bsky.social , @trevorbrandt.bsky.social, Karina, @shaharsu.bsky.social and @remenecker.bsky.social. www.nature.com/articles/s41...

Rational design of disordered proteins for sequence–function investigation - Nature

GOOSE enables the design and testing of thousands of disordered protein region sequences to reveal distinct sequence-to-function relationships.

nature.com

Alex Holehouse@alexholehouse.bsky.social · 5mo ago

New (well, very old, but 100% updated) preprint: Rational design of disordered proteins for systematic sequence-to-function investigation Work done in collaboration with @shaharsu.bsky.social lab - check out the three (3) threads from the folks who did the work!

Finally out - our work on high throughput design and characterization of disordered protein sequences 🪱🪱🪱. A long time collaboration with BFFs @alexholehouse.bsky.social and @remenecker.bsky.social, with experimental work led by @trevorbrandt.bsky.social and @karaehunt.bsky.social.

Rational design of disordered proteins for sequence–function investigation - Nature

GOOSE enables the design and testing of thousands of disordered protein region sequences to reveal distinct sequence-to-function relationships.

nature.com

Jim Shorter and his postdoc Miriam wrote a beautiful preview about our most recent paper on mRNAs preventing misfolding of IDR-containing proteins. UTR-ly unexpected: RNA chaperones tame intrinsically disordered proteins: Cell www.cell.com/cell/fulltex...

UTR-ly unexpected: RNA chaperones tame intrinsically disordered proteins

How do cells ensure that complex, multidomain proteins fold correctly? Luo et al. reveal a self-contained solution. The 3′UTR of an mRNA co-translationally chaperones the protein it encodes, preventin...

cell.com

Very happy to share a new preprint characterising the unfolded state of a folding-competent domain at the cusp of folding initiation on the ribosome. Co-led by @julianstreit.bsky.social from my PhD in John Christodoulou's lab. Many thanks to all the co-authors!

The initiation of de novo protein folding on the ribosome

How the earliest structure within the unfolded state is formed during biosynthesis on the ribosome and whether it has any consequences for downstream folding remain open questions. Here, we combine 15...

biorxiv.org

Deep-learning predictions of biomolecular structures : persistent limitations and new horizons extended by explicit ion addition https://www.biorxiv.org/content/10.64898/2026.07.24.740587v1

Latest preprint on AlphaFold potential and limitations. We look in particular at the addition of ions to models.

bioRxiv Biophysics@biorxiv-biophys.bsky.social · last wk.

Deep-learning predictions of biomolecular structures : persistent limitations and new horizons extended by explicit ion addition https://www.biorxiv.org/content/10.64898/2026.07.24.740587v1

We show, in collaboration with Yifan Dai, that biomolecular condensates function as inherent catalysts. Interphase potentials give rise to electric fields at the interfaces of condensates that are tunable, strong enough to align substrates, & function as electro catalysts. doi.org/10.1016/j.mo...

New publication with Chantal Prévost and @sacquin-mo.eurosky.social is out in JPCB ! We show with all-atom MD simulations that disordered alpha-tubulin C-terminal tails wrap around the proline-rich region of the Tau protein, but not so much around its repeat domains pubs.acs.org/doi/10.1021/...

Simulations of an Extended Tau/Tubulins Interface Reveal a Complex Disorder–Disorder Interplay Mediated by the C-Terminal Tails

Building on a complex between a tubulin protofilament (PF) and a fragment of the Tau protein containing residues 169 to 367, we investigate the dynamics of the disordered elements of the system, namely the tubulin C-terminal tails (CTTs) and the Tau protein, using classical all-atom molecular dynamics simulations. Our results show that CTTs adopt a hook-like dynamic pattern on the bare PF while remaining highly mobile. The binding of Tau on the PF surface alters the dynamics of the αI-CTTs in a sequence-dependent manner. While the repeat domains of Tau are mostly maintained on the PF by weak and strong binding patches with the tubulin cores, the Proline-Rich Region (PRR) relies on the wrapping phenomenon of αI-CTTs to fuzzily stabilize its interaction with the PF. Our study thus provides a deep dive into the dynamic interplay between the Tau protein and the CTTs of microtubules, the latter being characterized extensively using a variety of disorder-adapted metrics.

pubs.acs.org

Fantastic opportunity at @pasteur.fr in Spyros’ brand new lab, especially if you like protein design 🎉

Antigen Evolution & Design Lab@antigenevo.bsky.social · 2w ago

🚨 JOB ALERT🚨 We are very excited to be hiring the lab's ✨very first postdoc✨! Work on new AI technologies for decoding antigen protein evolution in a fresh research environment, at the heart of Paris 🇫🇷 Details & link to apply: research.pasteur.fr/en/job/postd... Deadline: Sep 1st

pHaseMD4AI: Phase-Space Dynamics Dataset with Chemical and pH Perturbations for Physically and Kinetically Consistent Biomolecular AI https://www.biorxiv.org/content/10.64898/2026.07.20.739474v1

Written by Esme Somerside Gregory and devised by Oxford student theatre company Cartesian Productions, 'Noether' chronicles the life of Emmy Noether, a major figure in 20th century mathematics #womeninscience #womeninSTEM youtu.be/4oMuV9XW-CQ?...

Noether

YouTube video by Oxford Mathematics

youtu.be

Cryo-EM structures of Alpha-Synuclein(31-100) amyloid fibrils reveal disease-like structural motifs without reproducing the Parkinson's Disease polymorph https://www.biorxiv.org/content/10.64898/2026.07.20.739490v1

Excited to share our recent preprint (biorxiv.org/content/10.6...), where we show that each of HP1α's binding partners (CAF-1, LBR, and Sgo1) tunes its phase separation differently, while electrostatic interactions ultimately dominate how phosphorylated HP1α forms condensates.

The role of electrostatic interactions in the phase separation of HP1α and its protein binding partners

Heterochromatin protein 1α (HP1α) is an intrinsic component of heterochromatin domains where it is involved in a diverse set of functions including heterochromatin spreading and organization, chromati...

biorxiv.org

Our new tool to analyze protein interfaces from MD trajectories is out in JMB, in its Computational Resources Special Issue! 🍀 Our tool, DynaPIN can be used to understand the biology of binding at the atomistic scale, as we have showed in its paper at doi.org/10.1016/j.jm... For more details👇👇👇

A. Berçin Barlas@aysebercinb.bsky.social · 3w ago

🎉 Finally out!! Our paper, "DynaPIN: A tool for characterizing dynamic protein interfaces" is accepted in JMB! @ezgikaraca.bsky.social (in collaboration with @sacquin-mo.eurosky.social & co.) DynaPIN is an open-source pipeline for analyzing dynamic protein interfaces. 🧵👇 📄 doi.org/10.1016/j.jm...

Coarse-grained simulations of long intrinsically disordered proteins: a benchmark of Martini 3 force-fields https://www.biorxiv.org/content/10.64898/2026.07.17.739185v1

Interested in trying it out for yourself? 🚀 Grab the code, check out the documentation, and start analyzing your own dynamic protein interfaces. We would love to hear your feedback! 💻 Code & documentation: github.com/CSB-KaracaLa...

GitHub - CSB-KaracaLab/DynaPIN: An open-source analysis toolkit to characterize dynamic protein interfaces from MD trajectories.

An open-source analysis toolkit to characterize dynamic protein interfaces from MD trajectories. - CSB-KaracaLab/DynaPIN

github.com