Hybrid simulations of stochastic reaction-diffusion processes for modeling intracellular signaling pathways

K.-H. Chiam, Chee Meng Tan, Vipul Bhargava, and Gunaretnam Rajagopal
Phys. Rev. E 74, 051910 – Published 14 November 2006

Abstract

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.

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  • Received 16 May 2006

DOI:https://doi.org/10.1103/PhysRevE.74.051910

©2006 American Physical Society

Authors & Affiliations

K.-H. Chiam*, Chee Meng Tan, Vipul Bhargava, and Gunaretnam Rajagopal

  • Bioinformatics Institute, 30 Biopolis Street, Singapore 138671, Singapore

  • *Electronic address: chiamkh@mailaps.org
  • Present address: Biomedical Engineering Department, Duke University, Durham, North Carolina 27708, USA.
  • Present address: Bioinformatics Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.

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Vol. 74, Iss. 5 — November 2006

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