Whole Cell Model
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- Last Updated: Wednesday, 25 January 2023 14:14
We are now entering the era of whole-cell simulations. Together with the group of Zan Luthey-Schulten we already modeled an entire cell (JCVI-Syn3a) at the Martini level of resolution. Featuring more than 60,000 proteins, millions of lipids and metabolites, 500 ribosomes and a 500 kbp circular dsDNA, more than 500 million CG beads in total.
For details, read our perspective paper: Stevens et al., 'Molecular dynamics simulation of an entire cell', Frontiers in Chemistry, vol 11, 2023. https://doi.org/10.3389/fchem.2023.1106495
The need for detailed models and dynamics of virus particles is clear, as part of our fight against pandemics such as COVID. Given the size and composition of typical viruses, the use of Martini to simulate their behavior is apparent. Indeed, viruses have already been targeted with Martini, including the capsid of the Cowpea Mosaic virus [1], and enveloped ones such as Influenza A virion [2], Dengue [3], and flavivirus [4]. More examples are reviewed in [5,6].
Intrinsically disorder proteins (IDPs) are an important class of proteins. Traditionally, the application of Martini to study IDPs has been limited due to the constraints in 2ndary structure imposed by an elastic network. However, the use of Go-potentials [1] as well as the use of SAXS constraints [2] offers more possibilities to capture the broad range of configurations characteristic of IDPs.
Polynucleotides (DNA, RNA) form a fundamental class of biomolecules. Given their importance, Martini models for both DNA [1] and RNA [2, see Figure depicting a Martini ribosome] have been developed. Parameters for nucleotide cofactors are also available [3,4], as well as a dedicated tool to analyze nucleoside packing [5]. Given the limitations of Martini with respect to modeling the directionality of hydrogen bonds, nucleotide folding and hybridization events can not be captured. As for the protein model, an elastic network is required to keep the overall structure in place.
Biomembranes are essential cellular components. Together with membrane-adhered structures, such as the cytoskeleton, cell membranes constitute incredibly heterogeneous and crowded environments, containing hundreds of different lipid types and being densely packed with a large variety of membrane proteins. They provide identity not only to the cell as a whole, through the enveloping plasma membrane, but also to many internal organelles.