Microbial Cell Modeling via Reacting/Diffusing Particles

Steve Plimpton and Alex Slepoy

We have developed a simulator called ChemCell that tracks protein interactions within cells and can be used to model signaling, metabolic, or regulatory response. Cell geometry is represented by triangulated membrane surfaces. Particles represent proteins, complexes, or other biomolecules of interest. They diffuse via 3d Brownian motion within the cytoplasm, or in 2d on membrane surfaces. When particles are near each other, they interact in accord with Monte Carlo rules to perform biochemical reactions which can represent protein complex formation and dissociation events, ligand binding, etc. ChemCell is an open-source research tool, designed to allow for easy experimentation with new modeling algorithms and options.

In this poster, we focus on the underlying algorithms used for reaction rules. We compare the original stochastic simulation algorithm (SSA) of Gillespie with approaches that enable a spatial component to be added to the SSA with varying degrees of rigor. We also highlight issues relevant to how reaction algorithms are implemented for parallel computation within ChemCell, with the eventual goal of enabling whole-cell models of realistic numbers of proteins and biomolecules. We illustrate use of simulator with simulations of the carbon-fixation process in Synechococcus, a seawater bacteria that is the focus of our DOE Genomes-to-Life project.

Support: This work was funded by the US Department of Energy's Genomics: GTL program (www.doegenomestolife.org) under project "Carbon Sequestration in Synechococcus Sp.: From Molecular Machines to Hierarchical Modeling" (www.genomes-to-life.org).