Hybrid simulations of stochastic reaction-diffusion processes for modeling intracellular signaling pathways.
In the intracellular environment, signaling takes place in a nonideal environment that is spatially heterogeneous and that is noisy, with the noise arising from the low copy numbers of the signaling molecules involved. In this paper, we model intracellular signaling pathways as stochastic reaction-diffusion processes and adapt techniques commonly used by physicists to solve for the spatiotemporal evolution of the signaling pathways. We then apply it to study two problems of relevance to the modeling of intracellular signaling pathways. First, we show that, in the limit of small protein diffusion which is typically the case for proteins in the cytosol crowded by other macromolecules, the extent of diffusion control, in the transient regime, on reactions is greater than previous predictions. Second, we show that the presence of scaffold proteins can modify the phosphorylation activity of a mitogen-activated protein kinase cascade, and explain how this activity is modulated by the scaffold protein concentration.
Chiam
K-H
KH
Bioinformatics Institute, 30 Biopolis Street, Singapore 138671, Singapore. chiamkh@mailaps.org
Tan
Chee Meng
CM
Bhargava
Vipul
V
Rajagopal
Gunaretnam
G
D000465:Algorithms; D002468:Cell Physiological Phenomena; D003198:Computer Simulation; D004058:Diffusion; D008954:Models, Biological; D015233:Models, Statistical; D009097:Multienzyme Complexes / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013269:Stochastic Processes
D009097:Multienzyme Complexes; D020543:Proteome