Luigi Scietti

Accurate Macromolecular Complex Modeling for Cryo-EM with CryoZeta pubmed.ncbi.nlm.nih.gov/41756897/ #cryoEM

A cryo-EM processing pipeline for microtubules using CryoSPARC https://www.biorxiv.org/content/10.64898/2026.02.24.703950v1

RE: https://fediscience.org/@Guillawme/111534984107819771

Something really cool happened to me this year!

@HRBridges re-processed a #cryoEM dataset from some previous work of mine and colleagues (publicly available as EMPIAR-10739; see quoted post below for a summary of this work). She […]

Our latest work is out in @science.org !!!!!!! We look into #chromatin condensates at near atomistic resolution to decipher its phase behaviour and material properties 👩‍🔬🥼🧬

I am pleased to announce the release of ProteinDJ v2! This is a major update that integrates BindCraft into the pipeline as an alternative to RFdiffusion for binder generation. You can try it out here: github.com/PapenfussLab/proteindj
#ProteinDJ #BindCraft #ProteinDesign @wehi-research.bsky.social

Multimodal deep learning integration of cryo-EM and AlphaFold3 for high-accuracy protein structure determination Communications Chemistry, Published online: 31 October 2025; doi:10.1038/s42004-025-01718-5Cryo-electron microscopy (cryo-EM) is a key technology for elucidating protein structures, yet automating high-accuracy structure building from cryo-EM maps remains challenging. Here, the authors present MICA, a deep learning approach integrating cryo-EM data with AlphaFold3 predictions, achieving superior accuracy and robustness, thus advancing automated protein structure determination.

Just out: Multimodal deep learning integration of cryo-EM and AlphaFold3 for high-accuracy protein structure determination

🚀 Introducing fully automated data processing for repeat-target #cryoEM.

Using new tools in #CryoSPARC, it is now possible to obtain resolutions & map quality equal to or better than manual processing, with zero user intervention.

Preprint: www.biorxiv.org/content/10.1...

Structures from AlphaFold3 - while often impressively good - tend to fail representing the dynamic ensembles accurately. And often parts of the structure are not correct. Adding experimental data, directly in AlphaFold's diffusion step, provides physically realistic protein ensembles. This image shows two cases where AlphaFold3-only structures were largely improved by guiding with experimental data.

📢 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. 🧵👇

Quote from Dr. Mingda Ye, University of Oxford, highlighting the collaborative breakthrough in cryo-EM imaging of small proteins: “This idea was initiated when solving sub-50kDa protein structures by cryo-EM was almost impossible. To break this barrier, many world-class scientists in different fields have combined forces and it is a great honour to work with them to bring this game-changing tool into reality!” The background diagram outlines the scientific workflow used in the study.

Exciting work from the Franklin, @ox.ac.uk, and @diamondlightsource.bsky.social has led to a new method for imaging small proteins (<50 kDa) using cryoEM. By using bifunctional, bispecific nanobody scaffolds, the team have successfully solved the smallest protein structure to date (14 kDa).

Collagen VI microfibril structure reveals mechanism for molecular assembly and clustering of inherited pathogenic mutations Nature Communications - Collagen VI microfibril cryo-EM structure resolves a cysteine-rich coiled-coil important for heterotrimerization and microfibril assembly, reveals a hotspot of collagen VI...

Amazing new paper from Clair Baldock's lab resolves the collagen VI microfibril structure by cryo-EM to reveal a cysteine-rich coiled-coil crucial for heterotrimerization & microfibril assembly. The structure also reveals a hotspot of collagen VI muscular dystrophy mutations that disrupt assembly.

We have written up a tutorial on how to run BindCraft, how to prepare your input PDB, how to select hotspots, and various other tips and tricks to get the most out of binder design!

github.com/martinpacesa...

🚀 Excited to release BoltzDesign1!

✨ Now with LogMD-based trajectory visualization.
🔗 Demo: rcsb.ai/ff9c2b1ee8
Feedback & collabs welcome! 🙌

🔗: GitHub: github.com/yehlincho/Bo...
🔗: Colab: colab.research.google.com/github/yehli...
@sokrypton.org @martinpacesa.bsky.social

A competitive regulatory mechanism of the Chd1 remodeler is integral to distorting nucleosomal DNA - Nature Structural & Molecular Biology Nodelman, Folkwein et al. define a regulatory region in Chd1 containing adjacent inhibitor and activator elements that compete for binding to the remodeler ATPase. The competition between these elemen...

New collaborative paper between JPArmache and Bowman (@bowmanlab-jhu.bsky.social) labs show how the yeast CHD1 chromatin remodeler depends on activator elements to distort nucleosomal DNA. This explains how the NegC inhibitor blocks activity. www.nature.com/articles/s41...

hu.MAP3.0: atlas of human protein complexes by integration of >25,000 proteomic experiments | Molecular Systems Biology imageimagehu.MAP3.0 integrates mass spectrometry experiments to identify human protein complexes. Using this resource, this study characterizes covariation of complexes, identifies mutually exclusive ...

Very excited that our work describing hu.MAP3.0 is published in @molsystbiol.org. Here we use machine learning to integrate >25k mass spectrometry experiments to place ~70% of human proteins into 15k protein complexes.

www.embopress.org/doi/full/10....

Amazing #cryoEM structures and incredible community here at @cniostopcancer.bsky.social for the “machines acting on DNA and RNA” congress!

I also had fun in making gummy GLT25D1 making #notthecover using #blender

This was a massive work from @fornerislab.bsky.social fellows to ehihc I contributed when I was Postdoc, and great #teamwork with Giorgio Colombo lab, @claudio-iacobucci.bsky.social and Alberta Pinnola lab.

we found that the GT1 domain, while not catalytic, is surprisingly capable of binding Ca²⁺ and UDP-α-galactose. This was intriguing to us, but all the mutants in the GT1 site did not produce folded protein, consistent with a structural role for the GT1 (also confirmed by MD).

And here the question: are they both active? which one is the responsible for the GalT activity? We combined #mutagenesis with #biophysics and #moleculardynamics to show that only the GT2 domain exhibits catalytic activity, facilitated by an unusual Glu-Asp-Asp motif critical for Mn²⁺ binding.

Each monomer contains two domains (GT1 and GT2) connected by a long but ordered linker. Surprisingly, both domains are capable of binding metal ions and the donor substrate UDP-α-galactose.

We solved the #Xray structure of GLT25D1/COLGALT1 via experimental phasing (yes, it was before #Alphafold) showing that it forms an elongated head-to-head homodimer

Collagen's function are ensured by essential post-translational modifications including galactosylation.
GLT25D1 is the galactosyltransferase enzyme responsible for initiating the glycosylation of hydroxylysine in collagen. but its structure was missing until now

Super happy to share the final shape of our work describing the molecular #structure and #enzymatic mechanism of human #collagen #galactosyltransferase #GLT25D1 published in @natcomms.nature.com. Want to know how collagen become sweet? read the 🧵 below!

Image processing for cryo-electron microscopy Cryo electron microscopy (cryo EM) is a major structural biology method for studying macromolecular complexes and cellular structures in their native states. Stable high resolution cryo microscopes, …

We are thrilled to announce the 2025 EMBO practical course in cryo-em image processing, Birkbeck College, London, 9-16 Sept 2025. More info & apply: meetings.embo.org/event/25-cry... Organisers Giulia Zanetti & Helen Saibil. Beautiful image from co-organizer @carolynmoores1.bsky.social lab.

This is a masterpiece ! #cryoEM

Structures of H2A.Z-associated human chromatin remodelers SRCAP and TIP60 reveal divergent mechanisms of chromatin engagement

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

Did you make our cryo-EM webinar last week? Dive into pre-processing, how to interpret 2D classes, 3D reconstructions from the initial map to final structure with CSO Giovanna Scapin.

Catch it here: youtu.be/2dBnPVkaoFs

Sign up for Overcoming Limitations, on 3/25: nimgs.zoom.us/webinar/regi...

📢 Registration is now open for 'Wellcome-MRC Cryo-EM in Structural Biology 2025'!

📅 Join us online March 3-7 at @diamondlightsource.bsky.social @universityofleeds.bsky.social for lectures & demos in #CryoEM & #CryoET: sample prep, SPA, model building & more!🧬

🔗 www.diamond.ac.uk/Instruments/...

Been thinking about creating a collection of good protein structure figures, as inspiration for my own work.

#1 www.nature.com/articles/s41...

gapTrick - Structural characterisation of protein-protein interactions using AlphaFold with multimeric templates The structural characterisation of protein-protein interactions is a key step in understanding the functions of living cells. Models of protein complexes provide important insights into interaction me...

I’m happy to share gapTrick, an AlphaFold2-based tool for characterising protein-protein complexes

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

#SIRT7 is a histone deacetylase with highly specific activity on #chromatin substrates.
We just published mechanism-based #cryoEM structures of #SIRT7 on nucleosomes to understand its activity 👇
www.nature.com/articles/s41...
(1/8) #ChemBio #ChemSky