Computational models for describing Ras nanocluster dynamics and PRMT5-mediated modulation

Abstract

The computational models implemented and exploited for the different analysis performed in the thesis "Spatiotemporal regulation of Ras-driven MAPK signaling: a stochastic and computational approach to Ras nanocluster dynamics and PRMT5-mediated modulation" were defined and simulated using a stochastic approach similar to Gillespie’s Stochastic Simulation Algorithm (SSA), in which the biochemical reactions of the signaling cascade are treated as a set of discrete stochastic events [1-3]. Each event is modeled as a Poissonian process with its occurrence frequency characterized by the corresponding reaction rate. All simulations were implemented in the Fortran programming language, specifically using the GNU Fortran 77 compiler. Two different basic configurations of the EGF-Ras-ERK MAPK signaling pathway have been modelled and simulated: i) a configuration based on the classical three-tiered cascade architecture comprising the core signaling module Raf-MEK-ERK, and ii) a configuration that localizes all pathway components and signaling events within discrete, membrane-associated nanoclusters. The different models are listed below