Now out as a perspective in PLOS Biology. Where next for structural bioinformatics? journals.plos.org/plosbiology/...

Joe Greener@jgreener64.bsky.social · 10mo ago

I wrote a blog post about the future of structural bioinformatics. Where to go after AlphaFold? How do we avoid the field becoming a load of half-baked LLMs? Let me know what you think. jgreener64.github.io/posts/struct...

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

AF-CALVADOS is now published doi.org/10.1002/pro.... We combine AlphaFold and CALVADOS to simulate flexible multidomain proteins at scale: — Ensembles of >12000 full-length human proteins — Comparison of IDRs alone and I n context for >1500 TFs @sobuelow.bsky.social @kejohansson.bsky.social

Happy to finally share that I will be starting my independent group at the @fmiscience.bsky.social in Feb 2027 in a vibrant new environment. We will use integrative in situ structural cell biology methods to investigate ciliary structure and dynamics in several model (and non-model 👀) systems!!

New online: Structures of protein folding intermediates on the ribosome

Structures of protein folding intermediates on the ribosome

Nature Structural & Molecular Biology, Published online: 16 June 2026; doi:10.1038/s41594-026-01814-7Atomistic structural ensembles of protein folding intermediates on the ribosome are resolved by comprehensive 19F nuclear magnetic resonance analyses integrated with molecular dynamics simulations, providing insights into cotranslational folding pathways.

dlvr.it

Blog post by Kamil Tamiola about our joint paper on On-the-fly Probability Enhanced Sampling in the multithermal ensemble to simulate IDPs idps.substack.com/p/a-disorder... Paper: doi.org/10.1038/s414... @julianstreit.bsky.social @invemichele.bsky.social & Sandro Bottaro

Now in Nature SMB: how do proteins fold while still being made? We solved all-atom structures of two ribosome-tethered folding intermediates—invisible to cryo-EM, seen only by ¹⁹F NMR. Thank you @julianstreit.bsky.social, John Christodoulou & co-authors! nature.com/articles/s41594-026-01814-7

Structures of protein folding intermediates on the ribosome - Nature Structural & Molecular Biology

Atomistic structural ensembles of protein folding intermediates on the ribosome are resolved by comprehensive 19F nuclear magnetic resonance analyses integrated with molecular dynamics simulations, pr...

nature.com

Excited to share our work describing structural ensembles of protein folding intermediates on the ribosome is now published in @natsmb.nature.com ! www.nature.com/articles/s41... Very grateful to co-first author @sammyhschan.bsky.social, our supervisor John Christodoulou and all our co-authors.

Structures of protein folding intermediates on the ribosome - Nature Structural & Molecular Biology

Atomistic structural ensembles of protein folding intermediates on the ribosome are resolved by comprehensive 19F nuclear magnetic resonance analyses integrated with molecular dynamics simulations, pr...

nature.com

Another banger

bioRxiv Biophysics@biorxiv-biophys.bsky.social · 3mo ago

Accurate protein stability prediction for small domains using mega-scale experiments https://www.biorxiv.org/content/10.64898/2026.05.19.726285v1

Why is it so difficult to predict accurate mutational effects on protein stability? We explored the contribution from changes in native state configurational entropy in this paper, which also happens to be the last from my PhD. A short thread of why this matters. 1/n doi.org/10.48550/arX...

arXiv q-bio.BM Biomolecules@qbiobm-bot.bsky.social · 3mo ago

Lindorff-Larsen, Best, Mittermaier, Kay, Dobson, Vendruscolo: Detection of residual native state entropy changes upon mutation in Fyn SH3 https://arxiv.org/abs/2605.14496 https://arxiv.org/pdf/2605.14496 https://arxiv.org/html/2605.14496

If you missed the preprint, now is a good time to read the journal version of @grocklin.bsky.social et al’s fantastic paper on multiplexed HDX measurements Large-scale discovery, analysis and design of protein energy landscapes doi.org/10.1038/s415...

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

Large-scale discovery, analysis, and design of protein energy landscapes https://www.biorxiv.org/content/10.1101/2025.03.20.644235v1

New preprint in which we built and simulated full-length models of α-Synuclein fibrils to reveal how the fuzzy coat mediates selective binding of peptides to amyloid fibrils Work led by Carlos Pintado-Grima in a nice collaboration with Salvador Ventura's lab doi.org/10.64898/202...

bioRxiv Bioinfo@biorxiv-bioinfo.bsky.social · 4mo ago

Full-Length Molecular Models of Brain-Derived α-Synuclein Fibrils Reveal a Fuzzy-Coat-Mediated Mechanism for Selective Peptide Binding https://www.biorxiv.org/content/10.64898/2026.04.16.718707v1

I am excited to share our most recent work collaborating with @centriolelab.bsky.social and @stearnslab.bsky.social to look at the ciliary base of mammalian multiciliated cells w/ cryo-ET, XL/MS, and U-ExM www.biorxiv.org/content/10.6...

Our latest @biorxivpreprint.bsky.social: "Prion-like transmission of human tau strains in the mouse brain" 🥳 With Michel Goedert and Masato Hasegawa. www.biorxiv.org/content/10.6...

New preprint on how disagreement among variant effect predictors can help guide prioritization of proteins for experimental analysis Work led by Nicolas F Jonsson in a collaboration with Joe Marsh. Preprint: doi.org/10.64898/202... @vxh357.bsky.social @jmarshlab.bsky.social 1/6

bioRxiv Bioinfo@biorxiv-bioinfo.bsky.social · 5mo ago

Disagreement among variant effect predictors guides experimental prioritization of target proteins https://www.biorxiv.org/content/10.64898/2026.03.18.712765v1

Check out our pre-print, where we train a protein and small molecule force field from scratch with a graph neural network. We show comparable performance to existing, manually-tuned force fields on a range of tasks including binding free energy prediction. (1/4) arxiv.org/abs/2603.16770

Training a force field for proteins and small molecules from scratch

Force fields for molecular dynamics are usually developed manually, limiting their transferability and making systematic exploration of functional forms challenging. We developed a graph neural networ...

arxiv.org

We are hiring a postdoc in computational biophysics and machine learning studies of intrinsically disordered proteins We aim to study the function of IDPs by combining CG MD, ML and bioinformatics in collaboration with @tanjamittag.bsky.social & @rhp-lab.bsky.social tinyurl.com/REWIRE-PD

Our recent investigation of the constriction in the bacterial ribosomal tunnel is online. Unbiased all-atom MD simulations of the entire ribosome and PDB analysis show, how flexible the constriction is. The flexibility is modulated by short nascent polypetides.

bioRxiv Biophysics@biorxiv-biophys.bsky.social · 5mo ago

Early nascent polypeptide dynamics are coupled to the flexibility of the ribosomal tunnel constriction https://www.biorxiv.org/content/10.64898/2026.03.10.710814v1

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

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...

bioRxiv Genetics@biorxiv-genetic.bsky.social · 6mo ago

Comprehensive Variant Effect Map of Parkin-Mediated Mitophagy in Parkinson's Disease https://www.biorxiv.org/content/10.64898/2026.02.09.704749v1

Really excited to share the latest work from my PhD with @giuliotesei.bsky.social and @lindorfflarsen.bsky.social!

Kresten Lindorff-Larsen@lindorfflarsen.bsky.social · 6mo ago

New preprint with work led by @asrauh.bsky.social in which we explore how double mutant cycles could be used to study molecular interactions in condensates, and highlight difficulties in extracting information about interactions from mutational experiments www.biorxiv.org/content/10.6...

New preprint with work led by @asrauh.bsky.social in which we explore how double mutant cycles could be used to study molecular interactions in condensates, and highlight difficulties in extracting information about interactions from mutational experiments www.biorxiv.org/content/10.6...

bioRxiv Biophysics@biorxiv-biophys.bsky.social · 6mo ago

On the Use of Double Mutant Cycles to Probe the Molecular Interactions in Biomolecular Condensates https://www.biorxiv.org/content/10.64898/2026.02.03.703500v1

Check out our newest preprint on how the chaperone BAG6 and E3 ligase RNF126 cooperate to target unstable and misfolded missense variants for degradation. Work led by Line Pedersen in @rhp-lab.bsky.social doi.org/10.64898/202...

Rasmus Hartmann-Petersen@rhp-lab.bsky.social · 6mo ago

Now on bioRxiv: genome‑wide CRISPR KO reveals BAG6 (chaperone) and RNF126 (E3) as core PQC for non‑native missense proteins. VAMP seq. shows >1000 Parkin variants are BAG6 targets, including known pathogenic variants. Work led by Line Pedersen. Collab with @lindorfflarsen.bsky.social

New preprint led by Fan Cao & Giulio Tesei We present a data-driven “stickiness” scale for amino acids in intrinsically disordered proteins 🍝, learned from SAXS data on 115 proteins. The scale captures effective residue interactions without conflating size and strength doi.org/10.64898/202...

bioRxiv Biophysics@biorxiv-biophys.bsky.social · 6mo ago

A stickiness scale for disordered proteins https://www.biorxiv.org/content/10.64898/2026.01.25.701651v1

Sampling IDPs is tough, but can be worth the effort! OPES multithermal made it a little easier for us, hopefully you'll find it useful as well

Julian Streit@julianstreit.bsky.social · 7mo ago

New preprint with @invemichele.bsky.social, Sandro Bottaro, Kamil Tamiola, and @lindorfflarsen.bsky.social on transiently structured states of IDPs sampled in atomistic simulations with enhanced sampling and integrated with experimental data.

New preprint with @invemichele.bsky.social, Sandro Bottaro, Kamil Tamiola, and @lindorfflarsen.bsky.social on transiently structured states of IDPs sampled in atomistic simulations with enhanced sampling and integrated with experimental data.

Kresten Lindorff-Larsen@lindorfflarsen.bsky.social · 7mo ago

Third preprint of the year is from @julianstreit.bsky.social who, with our collaborators at Peptone, show that multithermal On-the-fly Probability Enhanced Sampling (OPES) enables efficient generation of atomistic ensembles for disordered peptides and proteins 🍝 www.biorxiv.org/content/10.6...

We’re thrilled to share our latest iTP-seq protocol for mapping bacterial translation landscapes in vitro — with a complete experimental workflow streamlined by Mélanie Gillard and an open source Python library for data analysis developed by Thibaud Renault.

iTP-seq: a scalable profiling workflow to characterize bacterial translation landscapes in vitro

Nature Protocols - This protocol describes inverse toeprinting coupled to next-generation sequencing, an in vitro approach to characterize bacterial translation at codon resolution that can...

rdcu.be

Nature Protocols@natprot.nature.com · 7mo ago

New Article! iTP-seq: a scalable profiling workflow to characterize bacterial translation landscapes in vitro

First preprint of the year, led by Junjie Zhu from Haifeng Chen’s lab Extending Conformational Ensemble Prediction to Multidomain Proteins and Protein Complex doi.org/10.64898/202...

bioRxiv Bioinfo@biorxiv-bioinfo.bsky.social · 7mo ago

Extending Conformational Ensemble Prediction to Multidomain Proteins and Protein Complex https://www.biorxiv.org/content/10.64898/2026.01.14.699584v1

If anyone is interested in making bacterial ribosome-nascent chain complexes and studying them using HDX-MS, we have written up a detailed protocol. rdcu.be/eYFx4 Characterise the conformational dynamics of the ribosome, nascent polypeptide and bound chaperones, label-free and at peptide-level

We (@sobuelow.bsky.social & @kejohansson.bsky.social) tested AF-CALVADOS using the recently described PeptoneBench SAXS benchmark that contains SAXS data for >400 proteins with different amounts of order and disorder. The results look pretty good 😇 so we are sharing here while updating the preprint📝

Kresten Lindorff-Larsen@lindorfflarsen.bsky.social · 10mo ago

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/...