📢 New preprint:
Experiment-guided AlphaFold3 resolves accurate protein ensembles.
doi.org/10.1101/2025...

AlphaFold3 is incredible, but has crucial limitations: it typically collapses to a single conformation, ignoring the inherent dynamics of proteins. And it can be wrong. Here's a solution. 🧵👇

Initial attempt at replicating in relion (parameters in next post). This is for Aca2-RNA, using a 100k subset of the 2D-classified particles (no prior 3D cleanup).

A 1-class ab initio in relion, then local refinement in relion (1.8deg searches+blush) gives a nominally 3.3Å map; 3.5 Å w/out blush.

We finally wrote up the paper for LocScale-2.0.

edu.nl/pvhxv

Please try it out. LocScale is evolving & we are actively building in new features and improvements. Your feedback will help us shape the next steps.

Code: cryotud.github.io/locscale/

Work by @alok-bharadwaj.bsky.social and Reinier.

This one is a bit of a departure from the usual and definitely a work in progress!

We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below.

Read on for details... 1/x

Now published @cp-cellreports.bsky.social! Antibody-mediated TGF-β1 activation for the treatment of diseases caused by deleterious T cell activity: www.cell.com/cell-reports...
Fantastic collaboration & massive effort from Sophie Lucas Lab @ de Duve Institute. #CryoEM with @savvideslab.bsky.social.

We are excited to announce the first in-cell structure of a LINC complex within a native nuclear envelope at subnanometer resolution!! #In-cell cryo-ET + #atomistic MD simulations! @tomdendooven.bsky.social et al!!
www.biorxiv.org/content/10.1...

Finally out @natcomms.nature.com
"Single-domain antibodies directed against hemagglutinin and neuraminidase protect against influenza B viruses".
Great collab between @savvideslab.bsky.social (we performed #CryoEM) and Xavier Saelens Lab, spearheaded by Arne Matthys.

www.nature.com/articles/s41...

If this is true, it’s abysmally shortsighted for #NIH. The new tools nurtured by the long series of #CASP challenges probably contribute far more in one year to the scientific and industrial economies than the entire funds that have supported it.

We have a preprint for you

EHD2 forms rings on caveolae necks, in contrast to most EHDs forming helices. We determined its structure on membranes and show that N-term acts as a spacer

By Elena, Vasya @vasiliimikirtumov.bsky.social, Jeff &Oli Daumke www.biorxiv.org/content/10.1...

I’m very happy to share my first paper on the effects of AWI interactions and flexibility on SPA data quality! Thank you to everyone on the team 🤩

www.sciencedirect.com/science/arti...

We are happy to release LocScale2.0: a tool for context-aware, confidence-weighted cryoEM map optimisation.

Taking two half maps as input, LcoScale-2.0 produces feature-enhanced maps along with a robust confidence score that guides objective map interpretation.

cryotud.github.io/locscale/

Reports of diverse stoichiometries have complicated our understanding of the complex between ALK kinase and its #cytokine ligand ALKAL2. @janfelix.bsky.social @savvideslab.bsky.social &co reanalyze #cryoEM data to clarify the situation @plosbiology.org 🧪 plos.io/4lvRfvu

Delighted to share our reanalysis of cryo-EM data in EMPIAR-10930, now at:

journals.plos.org/plosbiology/... ;

revealing the ALK-ALKAL2 assembly with 2:1 stoichiometry and resolving the conundrum introduced by the originally reported 2:2 complex. ALK/LTK-cytokine signalling getting clearer!

#CryoSPARC v4.7 is out! 🚀 
Featuring a new automatic Micrograph Junk Detector that labels and rejects contaminants, new tools for curating subsets of particles, performance and stability fixes, and more!
Full changelog: cryosparc.com/updates

#cryoEM

I'm super happy that our story is now published!
📖 www.science.org/doi/10.1126/...
But what changed compared to the original preprint?

Also, I feel i should post Movie 1 🎥, that inspired the cover. Back when I did the original bluesky thread, movies were not available.

Foam film vitrification for cryo-EM https://www.biorxiv.org/content/10.1101/2025.03.10.642366v1

Structural biology is in an era of dynamics & assemblies but turning raw experimental data into atomic models at scale remains challenging. @minhuanli.bsky.social and I present ROCKET🚀: an AlphaFold augmentation that integrates crystallographic and cryoEM/ET data with room for more! 1/14.

New preprint from the @remaut-lab.bsky.social ! Happy to share our latest work on a new member of the ENA family, protein fibers found on the spore’s surface. Using CryoID @mikesleutel.bsky.social identified F-ENA in BTK. The paper dives deep into its structure analysis by integrating X-ray and AF3

Cryo-EM structures of mammalian membrane proteins from a single cell culture dish?

Yes, Micro ISOlation (MISO) sample preparation makes it possible.

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

Happy to be part of this exciting story and wonderful collaboration with the Rouslan Efremov lab.