Effects of Macromolecular Crowding on Genetic Networks
Effects of Macromolecular Crowding on Genetic Networks
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DOI：
10.1016/j.bpj.2011.10.053
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发表时间：
2011-12-21
影响因子：
3.4
通讯作者：
ten Wolde, Pieter Rein
中科院分区：
文献类型：
--
作者：
Morelli, Marco J.;Allen, Rosalind J.;ten Wolde, Pieter Rein
细胞内环境挤满了蛋白质、DNA和其他大分子。在生理条件下，大分子拥挤可以改变分子扩散和双分子反应的平衡，因此可能对生化网络的功能产生重大影响。我们提出了一种简单的方法来模拟大分子拥挤对生物化学网络的影响，通过适当的缩放双分子结合和解离率。我们使用这种方法，结合动力学蒙特卡罗模拟，分析拥挤对组成表达基因、抑制基因和噬菌体lambda遗传开关模型的影响，在存在和不存在转录因子与基因组DNA的非特异性结合的情况下。我们的研究结果表明，拥挤的影响主要是由结合-解离平衡的转移引起的，而不是蛋白质扩散的减缓，并且大分子拥挤可能对生化网络性能产生相关的和反直觉的影响。
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 lambda 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.