TY - CHAP
T1 - Replicating Chromosomes in Whole-Cell Models of Bacteria
AU - Gilbert, Benjamin R.
AU - Luthey-Schulten, Zaida
N1 - Publisher Copyright:
© The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature 2024.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Brownian dynamics
KW - Chromosome replication
KW - Chromosome segregation
KW - SMC proteins
KW - Whole-cell modeling
UR - http://www.scopus.com/inward/record.url?scp=85199126466&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85199126466&partnerID=8YFLogxK
U2 - 10.1007/978-1-0716-3930-6_29
DO - 10.1007/978-1-0716-3930-6_29
M3 - Chapter
C2 - 39028527
AN - SCOPUS:85199126466
T3 - Methods in Molecular Biology
SP - 625
EP - 653
BT - Methods in Molecular Biology
PB - Humana Press Inc.
ER -