Replicating Chromosomes in Whole-Cell Models of Bacteria

Area of Science:

• Computational biology
• Molecular biology
• Biophysics

Background:

• Accurate cell models require simulating genetic material replication.
• Previous models did not cover the entire cell cycle for bacterial chromosome replication.

Purpose of the Study:

• To develop a computational framework for modeling bacterial chromosome replication.
• To investigate chromosome organization changes during replication.
• To extend a whole-cell model (WCM) to the entire cell cycle for JCVI-syn3A.

Main Methods:

• Modeled bacterial chromosomes as polymers at 10 bp resolution using Brownian dynamics.
• Incorporated DNA mechanical properties (bending, torsional stiffness) and interactions with ribosomes.
• Augmented the polymer model with loop extrusion (SMC proteins) and topoisomerase action.
• Analyzed multi-fork replication states.

Main Results:

• Developed a realistic, cell-scale computational model of bacterial chromosomes.
• Simulated chromosome organization changes throughout the cell cycle.
• Integrated replication dynamics into a whole-cell model.

Conclusions:

• The computational framework enables comprehensive modeling of bacterial chromosome replication.
• This approach is crucial for understanding cell cycle dynamics and bacterial physiology.
• The model provides a foundation for further investigations into chromosome organization and function.