A Large Model Case Study: Solving CME for G1/S Checkpoint Involving the DNA-Damage Signal Transduction Pathway

Abstract

The main objective of this chapter is to investigate the performance of the ${\textit{ISP LOLAS}}$ algorithm on a large biochemical system. We analyse the state-space and probabilities of the species by implementing and integrating the mathematical model of the G1/S cell-cycle checkpoint involving the DNA-damage signal transduction pathway. The mathematical model is based on chemical kinetic principles for simulating pathways to show the dynamic behaviour of a cell cycle checkpoint pathway having reactive components. The cell cycle checkpoint pathways involve interactions between different enzymes and proteins in linked reactions. Most models developed for cell cycle checkpoints are quantitative, notably the G1/S checkpoint, which involves interactions between different proteins. They provide important information about the internal mechanisms and complex behaviour of cell cycle checkpoints.

In this chapter, we will briefly introduce the robustness of critical proteins of G1/S checkpoint involving the DNA-damage signal transduction pathway model in Sect. 6.1. In Sect. 6.2, we will prepare and integrate the model to our ${\textit{ISP LOLAS}}$ algorithm and, in Sect. 6.3, we analyse the state-space of the model and the performance of the ${\textit{ISP LOLAS}}$ algorithm using computational experiments. In Sect. 6.4, we provide a brief discussion and summary of the study and its results.