Replicating Chromosomes in Whole-Cell Models of Bacteria.

Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication of genetic material. In a recent study, we presented a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics. This approach was used to investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell cycle. To achieve cell-scale chromosome structures that are realistic, we modeled the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A. Additionally, the polymer interacts with ribosomes distributed according to cryo-electron tomograms of Syn3A. The polymer model was further augmented by computational models of loop extrusion by structural maintenance of chromosomes (SMC) protein complexes and topoisomerase action, and the modeling and analysis of multi-fork replication states.