Space in systems biology of signaling pathways – towards intracellular molecular crowding in silico

Abstract 

How cells utilize intracellular spatial features to optimize their signaling characteristics is still not clearly understood. The physical distance between the cell-surface receptor and the gene expression machinery, fast reactions, and slow protein diffusion coefficients are some of the properties that contribute to their intricacy. This article reviews computational frameworks that can help biologists to elucidate the implications of space in signaling pathways. We argue that intracellular macromolecular crowding is an important modeling issue, and describe how recent simulation methods can reproduce this phenomenon in either implicit, semi-explicit or fully explicit representation.

Abbreviations: 3D, three-dimensional, BD, Brownian dynamics, CA, cellular automata, DPD, dissipative particle dynamics, FCS, fluorescence correlation spectroscopy, FRAP, fluorescence recovery after photobleaching, GFRD, Green’s function reaction dynamics, HP, hydrophobic-polar, LB, lattice Boltzmann, MD, molecular dynamics, ODE, ordinary differential equation, PDE, partial differential equation

Keywords: Systems biology, Signaling pathway, Simulation, Molecular crowding, Excluded volume effect, Intracellular space