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Modeling Stochastic Kinetics of Molecular Machines at Multiple Levels: From Molecules to Modules

机译:在多个级别上建模分子机器的随机动力学:从分子到模块

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摘要

A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here.
机译:分子机器是单个大分子或大分子复合物。尽管这些天然纳米机器与它们的人造宏观机器之间有着惊人的表面相似性,但仍然存在着重大差异。活细胞中的分子机器在远离热力学平衡的等温环境中随机运行。在此小型审查中,我们提供了分子机器的目录以及从理论上对这些机器进行建模的基本工具箱的清单。工具包包括:1)用于对机器和机器驱动的过程进行建模的非平衡统计物理技术;和2),根据经验数据对功能机器进行逆向工程的统计推断方法。通常将该单元比作一个微型工厂,在该微型工厂中,机器以模块化的方式进行组织。每个模块由强耦合的多台计算机组成,但是不同的模块之间相互之间的交互作用较弱。该微型工厂拥有自己的自动化供应链和交付系统。受制于对单个分子机器建模的成功支持,我们主张在不久的将来将这些模型集成以开发功能模块的模型。从分子机制(机械组)的角度对细胞进行系统级描述可能会从我们在此处设想的进一步集成中出现。

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