Chelsea Brown

How do we build realistic cellular environments for simulations?

@cg-martini.bsky.social, @ma3ke.bsky.social, @janstevens.bsky.social answer this with Bentopy, an integration tool for proteomics, metabolomics, and structural data that rapidly assembles simulation-ready molecular models.

Building realistic models of cells means fitting proteins, RNA, and metabolites at experimental concentrations inside complex cellular architectures. Here's a movie showing how we pack the cytoplasmic space of the JCVI-Syn3A cell:

Cutaway and close-up views of a Martini coarse-grained whole-cell model of JCVI-syn3A, showing the densely packed cytoplasm with proteins, RNA, metabolites, and chromosome inside a lipid membrane with embedded membrane proteins

Our paper on [Bentopy](doi.org/10.1002/pro....) is out in Protein Science! We developed Bentopy to make assembling large-scale MD models more accessible, building on what we learned from trying to simulate whole-cell models. Here's our updated Martini JCVI-syn3A cell model👇

So pleased this is finally out! Wonderful work by the incredibly talented @ma3ke.bsky.social and @janstevens.bsky.social to generate densely packed systems, even with complex topologies

Go to the paper for cool science, stay for the mesmerizing figures 🤩

Read more about it in this thread 👇

It was great to be a small part of this work with the incredibly talented PhD student Andrea!!

If you want to find out how you can save heaps of time while still maintaining accurate results with CG metadynamics, look no further!! Read the article here 👇

My little outlook on how our lungs 🫁 are like the sea 🌊 is finally out in Central Science. Thanks to the support from incredible mentors @rommieamaro.bsky.social and @kprather.bsky.social !!

CCD2MD: A Suite of Packages for Preparing Co-Folded Outputs for Molecular Dynamics Simulations Protein–lipid interactions play a crucial role in the stability and function of membrane proteins. While experimental approaches to characterize these interactions in a native-like membrane environmen...

Kat Blow has developed CCD2MD, a suite of packages for preparing co-folded outputs for MD simulations.

Created for protein–lipid interactions in integral membrane proteins, it also works for peripheral and lipid-anchored proteins too.

pubs.acs.org/doi/full/10....

github.com/keb721/ccd2md

🎉🎉🎉 I can't wait to see what will come out of the Kearns Lab!! Congrats and good luck with getting everything off the ground!

Martini on top of the world ! TS2CG as a Membrane Builder | Journal of Chemical Theory and Computation pubs.acs.org/doi/10.1021/...

A true community effort ! The Martini 3 Lipidome: Expanded and Refined Parameters Improve Lipid Phase Behavior | ACS Central Science pubs.acs.org/doi/10.1021/...

An integrative modelling approach to the mitochondrial cristae - Communications Biology Integrative molecular modelling of a mitochondrial crista demonstrates a pipeline for constructing biologically representative systems and addressing interactions in complex environments.

@chelseabrown.bsky.social @cg-martini.bsky.social@rug.nl
Integrative molecular modelling of a mitochondrial crista demonstrates a pipeline for constructing biologically representative systems and addressing interactions in complex environments
www.nature.com/articles/s42...

It was great to help out the lipids with these two Mycobacterial enzymes. Fantastic work from the Mancia lab!

Thank you so much! Could you please drop the corresponding author (email address found with the manuscript) an email, and we can figure it out?

And in the next couple of weeks, I'm at the BPS thematic meeting Beyond Simple Models in Copenhagen and CCPBioSim in Southampton speaking about this work. Please come and say hello if you're around!

We provide this as a 'living model', to be added to and improved as we get more information and structures!

I have had such fun working on this and want to thank all of the authors, especially Tsjerk, with whom I had such long discussions about this!

Last but not least, we show how soluble components could be included in a model such as this by increasing the complexity. This creates defined matrix, intermembrane and cytoplasmic areas

The initial simulations provided us the chance to have a quick look at properties we can measure from simulations such as this

After this, it was time to put it all together and simulate! The entire model was ~4 million Martini particles with 651 protein chains!

The curvature of the inner mitochondrial membrane meant the assembly took a bit more care, but using Blender we created a map to place our proteins and lipids on in the right locations

Then came time to assemble both membranes found at a crista! The outer membrane was more straightforward to build, with a flat bilayer being a good approximation

All of the protein models were simulated on a smaller scale, to measure stability, membrane curvature and lipid interaction. The final poses with surrounding lipids could also be fed into the larger models

But there weren't always experimentally resolved structures to work off! The large subunit of MICOS was modelled with AlphaFold and verified using available biochemical data before including further in our models

First off, to get the structures of human mitochondrial membrane proteins, we used AlphaFold to complete experimental structures when chains or regions were missing

A stylized image of the molecular model of a mitochondrial crista, with proteins and lipids shown

What better way to use my first proper post than to share my first big piece of post-doctoral work with @cg-martini.bsky.social!
Here, we used integrative modelling to build and simulate a mitochondrial cristae.
Find the paper here (rdcu.be/eujAC) or see below for a quick overview 👇

Martini workshop registration now open !!!!
See cgmartini.nl for details and how to apply.
Looking forward to seeing you in Groningen, Aug 11-15th.

Pre-announcement: MARTINI tutorial workshop, August 11-15th 2025 in Groningen, The Netherlands !!
Learn basic and advanced Martini from the cocktail masters themselves. Registration will open soon.

MartiniGlass: a Tool for Enabling Visualization of Coarse-Grained Martini Topologies As molecular modeling gains ever more prominence in understanding cellular processes, high quality visualization of models and dynamics has never been more important. Naturally, much molecular visuali...

MartiniGlass: a Tool for Enabling Visualization of Coarse-Grained Martini Topologies | Journal of Chemical Information and Modeling pubs.acs.org/doi/10.1021/...