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/...

Beautiful picture looking out of the chemistry building at the University of Freiburg in Freiburg Germany. The old cathedral can be seen in the distance with a backdrop of a blue sky with clouds and distant foothills of the black forrest with fall colors showing through in the trees

picture of the Münster at dawn in the Altstadt of Freiburg, Germany, with a still dark sky in the background and moon over the Münster, in the foreground a well-lit flowers stand can be seen preparing for the daily morning market

I have a PhD position available in my lab at the University of Freiburg!! If you, or someone you know, might be looking for a position using modeling and simulations to uncover secrets in (glyco-)protein structure/function relationships please take a look at our website!
www.kearnslab.org

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

✨✨ 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 💪

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