Three-dimensional stochastic off-lattice model of binding chemistry in crowded environments.
Three-dimensional stochastic off-lattice model of binding chemistry in crowded environments.
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DOI：
10.1371/journal.pone.0030131
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Schwartz R
中科院分区：
文献类型：
--
作者：
Lee B;LeDuc PR;Schwartz R
分子拥挤是细胞内环境的特征之一，由不同种类的蛋白质和其他分子的密集混合物定义。与这些分子的相互作用显着改变了拥挤环境中化学反应的速率和平衡。活细胞的许多基本活动都受到拥挤效应的强烈影响，例如蛋白质折叠、蛋白质组装和分解、酶活性和信号转导。然而，定量预测拥挤将如何影响任何特定过程是一个非常具有挑战性的问题，因为许多物理和化学参数以难以简单分析的方式协同作用。为了针对这个问题建立更真实的模型，我们将先前的随机离格模型从二维 (2D) 空间扩展到三维 (3D) 空间，并检查 3D 结果与 2D 中的结果相比如何。我们表明，这两个模型都表现出质量相似的拥挤效应和相似的参数依赖性，特别是对于先前显示的对总反应平衡呈线性作用的一组参数。 2D 和 3D 模型之间存在定量差异，尽管随着系统从 2D 扩展到 3D，通常会采用渐进的非线性插值。然而，随着模拟盒厚度的增加，粒子的额外运动自由度会随着系统从 2D 移动到 3D 而产生显着的量变。更广泛参数范围的模拟结果进一步表明，分子拥挤的影响高度依赖于所检查的特定反应系统。
Molecular crowding is one of the characteristic features of the intracellular environment, defined by a dense mixture of varying kinds of proteins and other molecules. Interaction with these molecules significantly alters the rates and equilibria of chemical reactions in the crowded environment. Numerous fundamental activities of a living cell are strongly influenced by the crowding effect, such as protein folding, protein assembly and disassembly, enzyme activity, and signal transduction. Quantitatively predicting how crowding will affect any particular process is, however, a very challenging problem because many physical and chemical parameters act synergistically in ways that defy easy analysis. To build a more realistic model for this problem, we extend a prior stochastic off-lattice model from two-dimensional (2D) to three-dimensional (3D) space and examine how the 3D results compare to those found in 2D. We show that both models exhibit qualitatively similar crowding effects and similar parameter dependence, particularly with respect to a set of parameters previously shown to act linearly on total reaction equilibrium. There are quantitative differences between 2D and 3D models, although with a generally gradual nonlinear interpolation as a system is extended from 2D to 3D. However, the additional freedom of movement allowed to particles as thickness of the simulation box increases can produce significant quantitative change as a system moves from 2D to 3D. Simulation results over broader parameter ranges further show that the impact of molecular crowding is highly dependent on the specific reaction system examined.
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DOI：
10.1073/pnas.83.17.6258
发表时间：
1986-09-01
影响因子：
11.1
作者：
GRASBERGER, B;MINTON, AP;METZGER, H
通讯作者：
METZGER, H
影响因子：
15
作者：
Jiang, Ming;Guo, Zhihong
通讯作者：
Guo, Zhihong
影响因子：
4.8
作者：
Hatters, DM;Minton, AP;Howlett, GJ
通讯作者：
Howlett, GJ
影响因子：
2.9
作者：
Christiansen, Alexander;Wang, Qian;Wittung-Stafshede, Pernilla
通讯作者：
Wittung-Stafshede, Pernilla
影响因子：
3.3
作者：
Rosen, Jonathan;Kim, Young C.;Mittal, Jeetain
通讯作者：
Mittal, Jeetain