alexa Effects of macromolecular crowding on genetic networks.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Current Synthetic and Systems Biology

Author(s): Morelli MJ, Allen RJ, Wolde PR

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Abstract The intracellular environment is crowded with proteins, DNA, and other macromolecules. Under physiological conditions, macromolecular crowding can alter both molecular diffusion and the equilibria of bimolecular reactions and therefore is likely to have a significant effect on the function of biochemical networks. We propose a simple way to model the effects of macromolecular crowding on biochemical networks via an appropriate scaling of bimolecular association and dissociation rates. We use this approach, in combination with kinetic Monte Carlo simulations, to analyze the effects of crowding on a constitutively expressed gene, a repressed gene, and a model for the bacteriophage λ genetic switch, in the presence and absence of nonspecific binding of transcription factors to genomic DNA. Our results show that the effects of crowding are mainly caused by the shift of association-dissociation equilibria rather than the slowing down of protein diffusion, and that macromolecular crowding can have relevant and counterintuitive effects on biochemical network performance. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.
This article was published in Biophys J and referenced in Current Synthetic and Systems Biology

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