iSimBioSys: a discrete event simulation platform for 'in silico' study of biological systems

With the availability of huge databases cataloguing the various molecular "parts" of complex biological systems, researchers from multiple disciplines have focused on developing modeling and simulation tools for studying the variability of cellular behavior at a system level - encompassing the dynamics arising from many species of interacting molecules. In this work, we present a system engineering approach to model biological processes. In this approach, a biological process is modeled as a collection of interacting functions driven in time by a set of discrete events. We focus on the discrete event simulation platform, called "iSimBioSys", which we have developed for studying the dynamics of cellular processes in silico. As a test-bed for studying our approach we model the two component PhoPQ system, responsible for the expression of several virulence genes in Salmonella Typhimurium. We analyzed the effect of extra cellular magnesium on the behavioral dynamics of this pathway using our framework and compared the results with an experimental system. We also analyze the performance of iSimBioSys, based on the model biological system, in terms of system usage and response.