Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Tuesday Speaker Abstracts

SIMULATING A LIVING MINIMAL CELL: AN INTEGRATION OF EXPERIMENT, THEORY, AND SIMULATION Zaida Luthey-Schulten 1 ; 1 University of Illinois at Urbana-Champaign, Chemistry, Urbana, IL, USA We present a whole-cell fully dynamical kinetic model (WCM) of JCVI-syn3A, a minimal bacterial cell with a reduced genome of 493 genes that has retained few regulatory proteins or small RNAs. Cryo-electron tomograms provide the cell geometry and ribosome distributions. Time-dependent behaviors of concentrations and reaction fluxes from stochastic-deterministic simulations over a cell cycle reveal how the cell balances demands of its metabolism, genetic information processes, and growth, and offer insight into the principles of life for this minimal cell. The energy economy of each process including active transport of amino acids, nucleosides, and ions is analyzed. WCM reveals how emergent imbalances lead to slowdowns in the rates of transcription and translation. Integration of experimental data is critical in building a kinetic model from which emerges a genome-wide distribution of mRNA half-lives, multiple DNA replication events that can be compared to qPCR results, and the experimentally observed doubling behavior. Simulations are carried out using our GPU-based Lattice Microbes software for the spherical cells approximately 500 nm in diameter. References: Thornburg et al. “Fundamental behaviors emerge from simulations of a living minimal cell” , 2022, Cellhttps://doi.org/10.1016/j.cell.2021.12.025Gilbert et al. “Generating Chromosome Geometries in a Minimal Cell from Cryo-Electron Tomograms and Chromosome Conformation Capture Maps” 2021, Frontiers in Molecular Biosciences, https://doi.org/10.3389/fmolb.2021.644133T. M. Earnest, J. A. Cole, and Z. Luthey-Schulten. Simulating Biological Processes: Stochastic Physics from Whole Cells to Colonies Reports on Progress in Physics, 2018, doi:10.1088/1361- 6633/aaae2cM. J. Hallock, J. E. Stone, E. Roberts, C. Fry, Z. Luthey-Schulten Simulation of reaction diffusion processes over biologically-relevant size and time scales using multi-GPU workstations Parallel Comput. 2014, 40, 86-99, doi: 10.1016/j.parco.2014.03.009.

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