Alexander Taylor

Determining accurate conformational ensembles of intrinsically disordered proteins at atomic resolution Nature Communications - This study demonstrates how to combine molecular dynamics computer simulations with experimental biophysical data to determine accurate atomic-resolution ensembles of...

Our work developing a maximum entropy reweighting method to refine all-atom ensembles of IDPs with extensive NMR and SAXS datasets is now out in @natcomms.nature.com:

rdcu.be/eKlK7

Led by @dartmouthchem.bsky.social graduate student Kaushilk Borthakur in collaboration with @bonomimax.bsky.social

End GDP mania: how the world should really measure prosperity The obsession with economic output as a measure of human development puts sustainability on the back burner. Researchers can now help to devise better indicators.

The obsession with economic output as a measure of human development puts sustainability on the back burner

go.nature.com/4pNC96G

Excited to share a new preprint:

"Monomer binding modes of small molecules that modulate the kinetics of hIAPP amyloid formation"

by graduate student Michelle Garcia together with post-doc Korey Reid.

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

Code + Ensembles: github.com/paulrobustel...

Huntington’s disease treated for first time using gene therapy Preliminary results from a small trial offer the clearest evidence yet that the brain disease’s progression can be slowed.

A one-time gene therapy can markedly slow the progression of Huntington’s disease, potentially paving the way for the first ever treatment to alter the course of this rare, inherited brain disorder.

go.nature.com/4nu6YMs

Zn2+ Binding Shifts the Conformational Ensemble of α-Synuclein Monomers toward Accelerated Amyloid Formation Alpha-synuclein (αS) is an intrinsically disordered protein (IDP) that can self-assemble into amyloid fibrils, undergoing a transition from disordered monomers to ordered β-sheet-rich fibrils. The amy...

🚨 Excited to share our paper in JACS!
📈 We show that Zn²⁺ ions modulate the conformational ensemble of N-acetylated α-synuclein which directly influences its amyloidogenic behaviour.
🧩 Our approach combines ion mobility mass spec with ThT fluorescence, NMR and MD.
👉🏼 pubs.acs.org/doi/10.1021/...

PDB101: Molecule of the Month: Amyloids Alzheimer's disease and prion diseases are linked to unnatural aggregation of proteins into amyloid fibrils.

September 21 is #WorldAlzheimersDay
Alzheimer's disease and prion diseases are linked to unnatural aggregation of proteins into amyloid fibrils.

Front cover

Our review on CPEB and memory published today- thanks to all authors. Enjoy the read

Interactions with tau’s microtubule-binding repeats modulate amyloid-β aggregation and toxicity - Nature Chemical Biology The interplay between tau and amyloid-β (Aβ) in the development of Alzheimer’s disease is not fully understood. It has now been shown that tau’s microtubule-binding repeat regions, which contain a com...

Tau’s microtubule-binding repeat regions interact with amyloid-β (Aβ) to form hetero-assemblies, which can modify Aβ amyloidogenesis and alleviate Aβ-induced cytotoxicity

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

Image of paper cover

Interested in amyloid polymorphs? Our latest paper with PhD student Jack Connor is just out. Have a read and do try out his analysis on your favourite amyloid structures! doi.org/10.1016/j.st...

Navigating protein landscapes with a machine-learned transferable coarse-grained model - Nature Chemistry The development of a universal protein coarse-grained model has been a long-standing challenge. A coarse-grained model with chemical transferability has now been developed by combining deep-learning m...

Our development of machine-learned transferable coarse-grained models in now on Nat Chem! doi.org/10.1038/s415...
I am so proud of my group for this work! Particularly first authors Nick Charron, Klara Bonneau, Aldo Pasos-Trejo, Andrea Guljas.

Prediction of Small-Molecule Partitioning into Biomolecular Condensates from Simulation Predicting small-molecule partitioning into biomolecular condensates is the key to developing drugs that selectively target aberrant condensates. However, the molecular mechanisms underlying small-mol...

Huge congratulations to @alinaemelianova.bsky.social Pablo and Daniel on their paper on small-molecule partitioning into condensates now published in JACS Au and selected as ACS Editor’s Choice!!! pubs.acs.org/doi/full/10....

Accurate de novo design of high-affinity protein-binding macrocycles using deep learning - Nature Chemical Biology A method for de novo design of peptide macrocyles called RFpeptides has been developed. RFpeptides is an extension of RoseTTAFold2 and RFdiffusion and combines structure prediction and protein backbon...

A new paper from the Institute for Protein Design at UW presents RFpeptides, an extension of RoseTTAFold2 and RFdiffusion for de novo design of macrocyclic peptide binders

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

A new complexity in protein chemistry: Algorithm uncovers overlooked chemical linkages Proteins are among the most studied molecules in biology, yet new research from the University of Göttingen shows they can still hold surprising secrets. Researchers have discovered previously undetected ...

Researchers have discovered previously undetected chemical bonds within archived protein structures, revealing an unexpected complexity in protein chemistry.
phys.org/news/2025-0...

Looks useful:
CGBack: Diffusion Model for Backmapping Large-
Scale and Complex Coarse-Grained Molecular
Systems

Includes applications to reverse-CG/backmap multi-chain
molecular systems, including densely packed condensates.
doi.org/10.1101/2025...

Flow forces are widespread in both in vitro experiments and aggregation in vivo. Straight onto the reading list!

Thrilled to share our new paper on the front cover of JACS! 🧪💊🍾

Kinetic inhibitors of the early steps of #amyloid formation can profoundly affect the resulting fibril polymorphism – suggesting a new strategy to treat protein aggregation diseases.

🔗 pubs.acs.org/doi/10.1021/...

🧵... (1/6)

Figure showing the architecture of the CALVADOS package.

Do you like CALVADOS but are not quite sure how to make it?

We’ve got your back!

@sobuelow.bsky.social & @giuliotesei.bsky.social—together with the rest of the team—describe our software for simulations using the CALVADOS models incl. recipes for several applications. 1/5

doi.org/10.48550/arX...

Picture

At last our paper is out at JACS and we made the front cover! Thanks to Phospho animation for the image. See doi.org/10.1021/jacs....

🙌 Huge thanks to all authors, and to Phospho Biomedical Animation for the stunning cover!

📚 Full issue: pubs.acs.org/toc/jacsat/1...
📄 Paper: pubs.acs.org/doi/10.1021/...

@radford-lab.bsky.social @naranson.bsky.social

#amyloid #chemsky #diabetes #proteinaggregation

(6/6)

🔎 This reveals a possible new strategy to treat diseases involving amyloid formation – kinetic steering to divert aggregation down a less toxic route.

⚡ But it also suggests that formation conditions can kinetically, not just thermodynamically, determine fibril polymorphism in disease.

(5/6)

But then we had a surprise – cana and a related inhibitor also profoundly change the final structure of amyloid fibrils.

This suggests that early events in amyloid formation are crucial for determining the subsequent structures of fibril polymorphs.

(4/6)

Cana is already a type-2 diabetes drug with an unrelated mode of action, and may currently be given too late to affect islet amyloid formation.

But could earlier treatment with cana (or doxa) help to treat type-2 diabetes? We think these drugs are promising leads for future work.

(3/6)

This started as a drug repurposing study, asking whether existing drugs have untapped potential to treat IAPP amyloid formation, involved in type-2 diabetes.

Our repurposing screen identified two hits – canagliflozin (cana) and doxazosin (doxa) - which target early steps in aggregation.

(2/6)

Thrilled to share our new paper on the front cover of JACS! 🧪💊🍾

Kinetic inhibitors of the early steps of #amyloid formation can profoundly affect the resulting fibril polymorphism – suggesting a new strategy to treat protein aggregation diseases.

🔗 pubs.acs.org/doi/10.1021/...

🧵... (1/6)

Peregrine on the ledge of the Parkinson tower guarding over five eggs

High above the Parkinson steps, a pair of Peregrine Falcons are tending to five eggs!

Since 2008, Peregrine Falcons have been nesting intermittently on the Parkinson Tower. During that time, the University has seen fourteen chicks successfully hatch 🐣

‘Ageing’ cellular blobs could be linked to neurodegenerative diseases Over time biomolecular condensates' redox activity drops and tangled aggregates linked to conditions like Alzheimer's build-up

Biomolecular condensates are fluid blobs that form inside cells. New research finds that they can change the electrochemical gradients at their interfaces, changing their properties, @philipcball.bsky.social reports. #ChemSky

Oligomerization enables the selective targeting of intrinsically disordered regions by small molecules https://www.biorxiv.org/content/10.1101/2025.03.21.644603v1

Mount Everest, with tents in the foreground, on a sunny day

Today marks the first ever #WorldGlaciersDay ❄️

Glaciers are the water towers of the world, supplying freshwater to over half of humanity, but they are at the frontline of the climate crisis.

Find out about the important research and glacier initiatives that Leeds academics are involved with 👇🧊

CALVADOS now has parameters for phosphorylated amino acids

@asrauh.bsky.social @giuliotesei.bsky.social and Gustav Hedemark used a top-down approach in which we targeted experimental data to derive parameters or phosphorylated serine and threonine doi.org/10.1101/2025...

Delighted our latest paper on amyloid polymorphs is published in JACS- doi 10.1021/jacs.4c16743. Well done all- very proud!