New paper out in Protein Science!

We show that ligand binding in the substrate protein actively rewires Hsp90–cochaperone–client dynamics, steering protein fate rather than just stabilizing structures.

doi.org/10.1002/pro....

#ProteinScience #Proteostasis #Hsp90 #MolBio #CompBio

ReVesicle: Curation and Equilibration of Lipid Vesicles for Mesoscale Simulations Molecular dynamics simulations provide essential atomistic insights into the organization and dynamics of complex biological membranes. However, the equilibration of large-scale, curved lipid assemblies at the all-atom level remains a significant challenge. Standard construction approaches, such as wrapping planar bilayers onto spherical meshes, frequently reverberate into structural instabilities, including membrane holes, infiltrated water, lipid flipping, and nonequilibrated densities, which hinder stable production simulations. Here, we present ReVesicle, an iterative equilibration protocol designed to restore and stabilize quasi-spherical lipid vesicles with complex compositions and large dimensions. The proposed protocol combines selective identification and removal of infiltrated water molecules and flipped lipids with short nonequilibrium MD cycles and anisotropic pressure equilibration. These steps are organized into a modular, iterative sequence that progressively recovers bilayer continuity while preserving the vesicle geometry and enabling global density relaxation. Local vacuum-induced stress generated during nonequilibrium phases promotes lipid tail melting and hole curation, while anisotropic equilibration allows relaxation of box dimensions and system density. To demonstrate the robustness of ReVesicle, we applied the protocol to six biologically realistic vesicle systems: synaptic vesicles, plasma membranes, late endosomes, exosomes, mitochondria-derived vesicles, and the HIV-1 lipid envelope. These systems span diameters from 40 to 105 nm and reach total sizes of up to ∼150 million atoms with heterogeneous and asymmetric lipid compositions. Across all cases, ReVesicle consistently converges to continuous, tightly packed bilayers. Structural and biophysical analyses, including vesicle diameter, sphericity, area per lipid, and lipid acyl-chain order parameters, indicate preservation of quasi-spherical geometry and structural integrity. Overall, ReVesicle provides a reproducible framework for equilibrating large, heterogeneous lipid vesicles suitable for downstream all-atom simulations of complex biological environments.

We developed a reproducible protocol to automate the equilibration of mesoscale all-atom lipid vesicles, with systems reaching 150M atoms.

Grateful to @lcasalino88.bsky.social and @rommieamaro.bsky.social for their guidance.

Code: github.com/matteo-caste...
Paper: pubs.acs.org/doi/10.1021/...

While in Taipei at Academia Sinica for the #ISGC2026 symposium on grid and cloud computing, and giving a @bioexcelcoe.bsky.social #GANANA #HADDOCK workshop our HADDOCK portal passed the cap of 80000 registered users! Live stats at wenmr.science.uu.nl

Postdoc position:Computational Biophysics of Disordered Proteins, Lindorff-Larsen group, University of Copenhagen, Denmark https://tinyurl.com/REWIRE-PD Deadline May 3rd, 2026

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

How can we extract unbiased transition rates from ligand-unbinding Random Acceleration MD (RAMD) simulations? Our new paper lays out the theoretical framework behind RAMD. Take a look! doi.org/10.1063/5.03... @benoitroux.bsky.social @yiweiding.bsky.social & Alessia Ghidini #MD #drugdiscovery

Your protein moves, but when exactly? ⏱️
Meet eRMSF, our new Python tool that tracks fluctuations over time!

Traditional RMSF shows “how much.”
eRMSF shows “when.” 🔥

Preprint 🔗 doi.org/10.26434/che...
GitHub github.com/pablo-arante...
Try it on Colab → colab.research.google.com/github/pablo...

Regulation of N-glycosylation efficiency by eukaryotic oligosaccharyltransferase - Glycopedia Oligosaccharyltransferase (OST) catalyses the key step of N-glycosylation, transferring immature N-glycans to select Asn residues in nascent proteins in the endoplasmic reticulum (ER). Asn are more li...

Our work @benschulz.bsky.social on the specificity and the mechanism of activation of the eukaryotic oligosaccharyltransferase is now on Glycopedia ⬇️🎉🥳, the largest repository of #glycotime news and educational material online!

Thank you Serge Perez 🤓❤️

glycopedia.eu/2025/09/09/r...

Really proud of my sister’s sustainable knitwear business. She’s making some bold statement pieces! www.etsy.com/uk/shop/Grac...

MOLECULE: Molecular-dynamics and Optimized deep Learning for Entropy-regularized Classification and Uncertainty-aware Ligand Evaluation Machine learning (ML) and deep learning (DL) methodologies have significantly advanced drug discovery and design in several aspects. Additionally, the integration of structure-based data has proven to...

🚀 AI in drug discovery! We built a dual-modal deep neural net using 280 kinase structures to predict allosteric vs orthosteric ligands. Robust, dynamics-aware & fast — even with imputed data. 🔬 #AI #DrugDiscovery #CompChem pubs.acs.org/doi/10.1021/...

Design of multi-target peptide modulators for protein chaperone networks Essential chaperones heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90) collaborate in oncoprotein folding. Dual inhibition of these chap…

🚀New adventures in #DrugDiscovery: We designed multi-target leads that hit Hsp70, Hsp90 & Cdc37 at once—disrupting chaperone networks that fuel tumor growth. 🧬💥 Great collaboration with Mollapour @medmol.bsky.social and Gestwicki Labs
#CancerResearch #CompChem

shorturl.at/gGk7m

Integrating deep learning for post-translational modifications crosstalk on Hsp90 and drug binding Post-translational modification (PTM) of proteins regulates cellular proteostasis by expanding protein functional diversity. This naturally leads to increased proteome complexity as the result of PTM ...

Just out in Journal of Biological Chemistry!
Our latest paper uses deep learning to dissect PTM crosstalk on Hsp90 and its role in drug binding.
Proud of this team effort! www.jbc.org/article/S002...

We are looking for someone to join the group as a postdoc to help us with scaling implicit transfer operators. If you are interested in this, please reach out to me through email. Include CV, with publications and brief motivational statement. RTs appreciated!

Evolutionary Dynamics and Functional Differences in Clinically Relevant Pen β-Lactamases from Burkholderia spp. Antimicrobial resistance (AMR) is a global threat, with Burkholderia species contributing significantly to difficult-to-treat infections. The Pen family of β-lactamases are produced by all Burkholderi...

In our latest work, we look into how the dynamics of four very similar, and clinically important β lactamase enzymes from Burkholderia have evolved to generate very different substrate profiles.
@ucllifesciences.bsky.social

Design principles of cell-state-specific enhancers in hematopoiesis Screen of minimalistic enhancers in blood progenitor cells demonstrates widespread dual activator-repressor function of transcription factors (TFs) and enables the model-guided design of cell-state-sp...

Out in Cell @cp-cell.bsky.social: Design principles of cell-state-specific enhancers in hematopoiesis
🧬🩸 screen of fully synthetic enhancers in blood progenitors
🤖 AI that creates new cell state specific enhancers
🔍 negative synergies between TFs lead to specificity!
www.cell.com/cell/fulltex...
🧵

Once again, a great collaboration between the Buchner Lab, the @sattler-lab.bsky.social and the Rosenzweig Lab!

Protonated Glutamate and Aspartate Side Chains Can Recognize Phosphodiester Groups via Strong and Short Hydrogen Bonds in Biomacromolecular Complexes Phosphodiester groups occur ubiquitously in nature, e.g. in nucleic acids or in cyclic (di-)nucleotides important for signal transduction. Proteins often use polar or positively charged amino acids t...

You thought Glu/Asp don't like RNA or DNA? Maybe you even introduced them into your protein to stop such interactions?
😱🧪
Think again! New paper @angewandtechemie.bsky.social with Wöhnert lab shows structural context matters for phosphodiester interactions!
onlinelibrary.wiley.com/doi/10.1002/...

Pathogenic mutation impairs functional dynamics of Hsp60 in mono- and oligomeric states Nature Communications - Mutations cause impairment of function in the chaperone Hsp60. Here, the authors investigate their impact with MD simulations from the monomer to the 28-mer complex, and...

Read our latest #research on #Chaperones, #Mutations, #Function Emergence in large compllexes, published with @SpringerNature in Nature Communications. #CompChem #CompBiol #ChaperoneCode

rdcu.be/ehmjZ

Modular synthesis of functional libraries by accelerated SuFEx click chemistry Accelerated SuFEx Click Chemistry (ASCC) is a powerful method for coupling aryl and alkyl alcohols with SuFEx-compatible functional groups. With its hallmark favorable kinetics and exceptional product...

Our article in @chemicalscience.rsc.org registers as one of the most popular articles of 2024. The study on Sufex click chemistry was led by John Moses @cshlnews.bsky.social

Pathogenic mutation impairs functional dynamics of Hsp60 in mono- and oligomeric states - Nature Communications Mutations cause impairment of function in the chaperone Hsp60. Here, the authors investigate their impact with MD simulations from the monomer to the 28-mer complex, and show the pervasive effects of ...

Happy to share our latest paper in @naturecomms.bsky.social. We show how pathogenic mutation V72I disrupts dynamics, rewiring allosteric routes and impairing function in chaperone Hsp60 from the monomer to large complexes. #CompChem #MolecularBiology

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

Google Colab

Run BioEmu in Colab - just click "Runtime → Run all"! Our notebook uses ColabFold to generate MSAs, BioEmu to predict trajectories, and Foldseek to cluster conformations.
Thanks @jjimenezluna.bsky.social for the help!
🌐 colab.research.google.com/github/sokry...
📄 www.biorxiv.org/content/10.1...

✨✨ It's #glycotime for #HIV Env ✨✨

N-linked glycans modulate flexibility & MPER epitope exposure #glycotime

Huge effort by @shehata92.bsky.social @lcasalino88.bsky.social with cryoET of Env in VLPs by @thevillalab.bsky.social & team 💪

Would love feedback!

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

Enzyme Enhancement Through Computational Stability Design Targeting NMR-Determined Catalytic Hotspots Enzymes are the quintessential green catalysts, but realizing their full potential for biotechnology typically requires improvement of their biomolecular properties. Catalysis enhancement, however, is often accompanied by impaired stability. Here, we show how the interplay between activity and stability in enzyme optimization can be efficiently addressed by coupling two recently proposed methodologies for guiding directed evolution. We first identify catalytic hotspots from chemical shift perturbations induced by transition-state-analogue binding and then use computational/phylogenetic design (FuncLib) to predict stabilizing combinations of mutations at sets of such hotspots. We test this approach on a previously designed de novo Kemp eliminase, which is already highly optimized in terms of both activity and stability. Most tested variants displayed substantially increased denaturation temperatures and purification yields. Notably, our most efficient engineered variant shows a ∼3-fold enhancement in activity (kcat ∼ 1700 s–1, kcat/KM ∼ 4.3 × 105 M–1 s–1) from an already heavily optimized starting variant, resulting in the most proficient proton-abstraction Kemp eliminase designed to date, with a catalytic efficiency on a par with naturally occurring enzymes. Molecular simulations pinpoint the origin of this catalytic enhancement as being due to the progressive elimination of a catalytically inefficient substrate conformation that is present in the original design. Remarkably, interaction network analysis identifies a significant fraction of catalytic hotspots, thus providing a computational tool which we show to be useful even for natural-enzyme engineering. Overall, our work showcases the power of dynamically guided enzyme engineering as a design principle for obtaining novel biocatalysts with tailored physicochemical properties, toward even anthropogenic reactions.

Our latest paper "Enzyme Enhancement Through Computational Stability Design Targeting NMR-Determined Catalytic Hotspots" now out in JACS @jacs.acspublications.org. Collaboration with Jose M. Sanchez-Ruiz in Granada, among others. pubs.acs.org/doi/full/10....

This sounds great. Also, what a lot of questions visualizations like this raise. Don't you think, @bnerlich.bsky.social?

One‐pot dual protein labeling for simultaneous mechanical and fluorescent readouts in optical tweezers Optical tweezers are widely used in the study of biological macromolecules but are limited by their one-directional probing capability, potentially missing critical conformational changes. Combining ...

Out now! Our latest paper where we show a "one-pot" labelling technique which allows for simultaneous mechanical and fluorescent readouts from a protein (Hsp90):
onlinelibrary.wiley.com/doi/10.1002/...
Congratulations to everyone who worked on this, especially Laura!

Point mutations of the mitochondrial chaperone TRAP1 affect its functions and pro-neoplastic activity Cell Death & Disease - Point mutations of the mitochondrial chaperone TRAP1 affect its functions and pro-neoplastic activity

Read our latest research with the Rasola Lab and @elenapapaleo.bsky.social on how mutations on the mitochondrial protein TRAP1 impact its function and cancer related activities, published with
@springernature on Cell Death and Disease in rdcu.be/edidL

Happy to share our latest work "Large-scale energy decomposition for the analysis of protein stability". We use simple simulations to predict the impact of mutations on stability of more than 250 mutants in different folds. doi.org/10.1016/j.cs...
#CompChem #CompBiol #AI #Biotechnology

Please check it out - postdoc is available in Struct Biol for Drug Discovery in Cancer in my group at IIT.

Great project with potential for impactful results, papers and more ...

iit.taleo.net/careersectio...

Pumped about #MachineLearning the adaptive exact exchange admixture in hybrid #DFT approximations: It can even cure the infamous spin-gap problem (see below). Just out in @ScienceAdvances with D Khan, A Price, B Huang and M Ach! @uoft.bsky.social #CompChem www.science.org/doi/10.1126/...

Our research group CompOpt from the Università degli Studi di Pavia participated at the 3rd Workshop of the UMI Group Math4AIML in Bari, contributing with talks and posters on the latest developments in optimization and data science

@famo2spaghi.bsky.social @davideduma.bsky.social