Simulations of Replication and Translation on the Whole Cell Level

Zaida Luthey-Schulten, University of Illinois at Urbana-Champaign

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Prior to cell division, microorganisms construct a second copy of their chromosome (replication) containing every gene, including those that encode the ribosome—the RNA:protein complex universally responsible for protein synthesis. Recent experiments in vitro and in vivo are revealing detailed mechanisms for chromosome replication and ribosome biogenesis. However, a whole cell level description of these two universally conserved processes is still missing. Our goal is to construct kinetic models for chromosome replication and ribosome biogenesis that reproduce and extend experimental observations. Stochastic simulations of the validated models will then be performed in order to understand cellular level behaviors of both processes. In particular, we propose to continue two projects to be conducted on Blue Waters. The first focuses on detailed modeling of the dynamics and spatial heterogeneity of CtrA—a key regulator of chromosomal replication and cell-cycle timing—in Caulobacter crescentus. Our GPU-accelerated Lattice Microbes stochastic simulation software will be used. The second project studies the assembly of the pre-30S ribosomal complex which forms from the interactions between ribosomal signatures in 5´ and central domain on the small subunit. All-atom molecular dynamics simulations will be conducted to explore key steps in the ribosome assembly process. Assembly intermediates obtained from the kinetic model of ribosome biogenesis will be tested by molecular dynamics simulations to provide further details of the conformational rearrangements during assembly.