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. 2023 Jan 18:11:1106495.
doi: 10.3389/fchem.2023.1106495. eCollection 2023.

Molecular dynamics simulation of an entire cell

Jan A Stevens  1 , Fabian Grünewald  1 , P A Marco van Tilburg  1 , Melanie König  1 , Benjamin R Gilbert  2 , Troy A Brier  2 , Zane R Thornburg  2 , Zaida Luthey-Schulten  2 , Siewert J Marrink  1
Affiliations

Molecular dynamics simulation of an entire cell

Jan A Stevens et al. Front Chem. .

Abstract

The ultimate microscope, directed at a cell, would reveal the dynamics of all the cell's components with atomic resolution. In contrast to their real-world counterparts, computational microscopes are currently on the brink of meeting this challenge. In this perspective, we show how an integrative approach can be employed to model an entire cell, the minimal cell, JCVI-syn3A, at full complexity. This step opens the way to interrogate the cell's spatio-temporal evolution with molecular dynamics simulations, an approach that can be extended to other cell types in the near future.

Keywords: JCVI-syn3A; Martini force field; coarse grain; integrative modeling; minimal cell; polyply.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Integrative modeling workflow for building in silico whole-cell models. The initial step consists of collecting experimental data to inform the in silico modeling. Data from CryoET images [Image from EMD-23661 by Lam and Villa ref. (Gilbert et al., 2021)], Cryo-EM protein structures and -Omics experiments are incorporated into our cell models. The second stage in the workflow concerns mesoscale modeling. Here a kinetic model of the whole JCVI-syn3A [Image ref. (Thornburg et al., 2022) is used to gain quantitative insights into cellular processes and composition. As part of the final step, Martini models of the cellular components are generated using tools in the Martini ecosystem: Polyply, Martinize2, and TS2CG (Image ref. (Pezeshkian et al., 2020)]. Lastly, Bentopy facilitates the assembly of the individual molecular components in their appropriate abundances into the final molecular-resolution whole-cell model.
FIGURE 2
FIGURE 2
Whole-cell Martini model of JCVI-syn3A. The four stages of cell building are shown on the side. The final system contains 60,887 soluble proteins (light blue), 2,200 membrane proteins (blue), 503 ribosomes (orange), a single 500 kbp circular dsDNA (yellow), 1.3 million lipids (green), 1.7 million metabolites (dark blue), 14 million ions (not shown) and 447 million water beads (not shown) for a total of 561 million beads representing more than six billion atoms. Image rendered with Blender (Blender Online Community, 2022).
See this image and copyright information in PMC

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