Replicating Chromosomes in Whole-Cell Models of Bacteria

Benjamin R. Gilbert, Zaida Luthey-Schulten

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages625-653
Number of pages29
DOIs
StatePublished - 2024

Publication series

NameMethods in Molecular Biology
Volume2819
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Brownian dynamics
  • Chromosome replication
  • Chromosome segregation
  • SMC proteins
  • Whole-cell modeling

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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