Ceramide – VDAC1 binding in a membrane

The role of mitochondria in apoptosis is well established, and a number of protein–protein interactions in its outer membrane has been linked to apoptotic pathways. The VDAC (voltage- dependent anionic channels) family of proteins is central to this binding, having been implicated in the retention of apoptotic proteins in the outer mitochondrial membrane [1] and self-oligomerization [2] — an event also linked to apoptosis. In a recent study we have ascertained that ceramide binds VDAC proteins (via a binding site involving VDAC1’s Glu73) and that such binding somehow triggers apoptosis [3]. An immediate hypothesis is that the presence of ceramide affects the binding profile of VDAC and promotes apoptosis-associated oligomerizations. Since that work was done using the (now outdated) Martini 2 model, we will recreate in this tutorial the same ceramide binding simulations, but using the state-of-the-art Martini 3 model [4].

Throughout this tutorial, you will gain experience in performing an MD simulation using CG resolution (Martini Force Field). To get started, follow the steps in the Google Colab notebook found in the following repository: https://github.com/martincalvelo/MARTINI-CG-TUTORIALS/tree/main/1-Ceramide%E2%80%93VDAC1_binding_in_a_membrane

1 – Sci. Rep. 6, 32994; doi: 10.1038/srep32994 (2016)

2 – Mol. Cell. Biol. 30, 5698; doi: 10.1128/MCB.00165-10 (2010)

3 – Nat. Commun. 10, 1832; doi: 10.1038/s41467-019-09654-4 (2019) 

4 – Nat.Methods 18, 382; doi: 10.1038/s41592-021-01098-3 (2021)