Discrete diffusion models to study the effects of Mg2+ concentration on the PhoPQ signal transduction system

BMC Genomics

Research

Preetam Ghosh¹  Chaoyang Zhang¹  Sajal K Das²  Samik Ghosh²  Kalyan Basu² 

[1] Computational Biology and Bioinformatics Lab, School of Computing, The University of Southern Mississippi, USA;Department of Computer Science and Engineering, The University of Texas at Arlington, USA;

关键词: Discrete Event;    Discrete Event Simulation;    Molecular Transport;    System Biology Markup Language;    Chemical Master Equation;   

DOI  :  10.1186/1471-2164-11-S3-S3

来源: Springer

【 摘 要 】

BackgroundThe challenge today is to develop a modeling and simulation paradigm that integrates structural, molecular and genetic data for a quantitative understanding of physiology and behavior of biological processes at multiple scales. This modeling method requires techniques that maintain a reasonable accuracy of the biological process and also reduces the computational overhead. This objective motivates the use of new methods that can transform the problem from energy and affinity based modeling to information theory based modeling. To achieve this, we transform all dynamics within the cell into a random event time, which is specified through an information domain measure like probability distribution. This allows us to use the “in silico” stochastic event based modeling approach to find the molecular dynamics of the system.ResultsIn this paper, we present the discrete event simulation concept using the example of the signal transduction cascade triggered by extra-cellular Mg2+ concentration in the two component PhoPQ regulatory system of Salmonella Typhimurium. We also present a model to compute the information domain measure of the molecular transport process by estimating the statistical parameters of inter-arrival time between molecules/ions coming to a cell receptor as external signal. This model transforms the diffusion process into the information theory measure of stochastic event completion time to get the distribution of the Mg2+ departure events. Using these molecular transport models, we next study the in-silico effects of this external trigger on the PhoPQ system.ConclusionsOur results illustrate the accuracy of the proposed diffusion models in explaining the molecular/ionic transport processes inside the cell. Also, the proposed simulation framework can incorporate the stochasticity in cellular environments to a certain degree of accuracy. We expect that this scalable simulation platform will be able to model more complex biological systems with reasonable accuracy to understand their temporal dynamics.

【 授权许可】

CC BY   
© Ghosh et al; licensee BioMed Central Ltd. 2010