Fabian Grünewald

Coarse-Grained Martini 3 Model of Chondroitin Sulfate A Chondroitin sulfate A (CSA) is a negatively charged linear glycosaminoglycan that plays a vital role in many biological processes. Research on CSA has been challenging due to its size, chemical heterogeneity, and multitude of binding partners. To address these issues, we developed a model of CSA for coarse-grained molecular dynamics simulations based on the Martini 3 force field. We demonstrate that this model is capable of reproducing atomistic properties of the repeating CSA disaccharide unit, including its molecular volume, bonded interactions, and structural polymer properties of CSA chains of different lengths. In particular, for biologically relevant long chains and despite using an explicit solvent, the computational cost is significantly reduced, relative to the cost equivalent atomistic simulations would require. The compatibility of the model with the Martini Go̅ protein model was tested by retrieving the force–response relationship of the CSA–malaria adhesin VAR2CSA complex. Importantly, we explored the influence of electrostatics on CSA aggregation. We show that the default Martini 3 parameters lead to overaggregation. We provide at least three different strategies to alleviate this issue, making use of a bigger bead for sodium cations, reflecting their hydration shell, partial ionic charges as a mean-field resource to take into account electronic polarizability, and, optionally, particle mesh Ewald summation as a more robust treatment of long-range electrostatics. Our model enables predictive modeling of CSA and potentially other chondroitin sulfates with the Martini 3 force field. In addition, this model provides insights for the further development of coarse-grained models of highly charged systems.

🧪 Simulating large biomolecules without massive compute costs

This new study from the group Frauke Gräter presents a coarse-grained model of chondroitin sulfate A (CSA) using the Martini 3 framework.
pubs.acs.org/doi/10.1021/...

@mpip-mainz.mpg.de @hitsters.bsky.social

New preprint: “When lipids embrace RNA”

www.biorxiv.org/content/10.6...

Using multiscale simulations (🍸 #Martini + constant-pH MD), we show that:

• Local pKa ≠ global pKa
• Endosomal escape is limited by persistent protonation.

#LNP #MolecularDynamics

Wie die Industrie den Rhein mit unbekannten Stoffen verschmutzt Der Rhein gilt heute wieder als sauber. Doch unsere Recherche entlarvt einen mysteriösen Chemiecocktail im längsten deutschen Fluss. Die Industrie darf massenweise völlig unbekannte Schadstoffe einlei...

Der #Rhein gilt als sauber. Doch im Wasser schwimmen Zehntausende #Chemikalien, bei vielen kennt niemand die Wirkung. Grenzwerte gelten oft nur für Bekanntes. Was heißt das fürs #Trinkwasser von Millionen?

Very happy to see our recent work featured on the cover of the Journal of Chemical Theory and Computation 🎉
A long journey with many people involved — grateful to everyone who helped make this happen.

Paper: pubs.acs.org/doi/10.1021/...

@pubs.acs.org #MyACSCover #JCTC #Martini3

Martini 3 Building Blocks for Lipid Nanoparticle Design Lipid nanoparticles (LNPs) represent a promising platform for advanced drug and gene delivery, yet optimizing these particles for specific cargos and cell targets poses a complex multifaceted challeng...

Martini 3 Building Blocks for Lipid Nanoparticle Design | Journal of Chemical Theory and Computation pubs.acs.org/doi/full/10....

New on the Martini webportal (cgmartini.nl/docs/contact...): acknowledgment of all the people who contribute to the development. The list is still growing - if you feel your name should be added please let us know.

HITS-SIMPLAIX Colloquium: Rommie Amaro on Computational Microscopy for In Situ Molecular Dynamics YouTube video by TheHITSters

Ever wondered what microscopic passengers you send out when you talk or sing? 🗣️💨

Rommie Amaro showed how viruses and more hitch a ride and how data-centric simulations give us atomic-scale views of these tiny travelers.

Ready to zoom in? Watch now on YouTube: www.youtube.com/watch?v=96KH...

Try out the code for yourself:
💻 github.com/wilsonjcarte...

Cool stuff. Has it been tested for Martini3 proteins?