动态校对
Allostery and Kinetic Proofreading
摘要：
动力学校对是存在于中心法则和超越中心法则的过程中的纠错机制，并且通常需要核苷酸水解的自由能来进行其操作。虽然许多生物学校对方案的分子参与者是已知的，但我们对能量消耗如何管理以促进保真度的理解仍然不完整。在我们的工作中，我们介绍了一种替代的概念方案，称为“活塞模型的校对”，通过水解酶的激活被取代的变构激活实现通过机械工作的活塞上的监管配体。受费曼的棘轮和棘爪机制的启发，我们考虑了一种机械发动机，其设计用于驱动由降低重量提供动力的活塞动作，其功能类似于细胞中的ATP合成酶。由于其机械设计，活塞模型允许我们调整驱动引擎的“旋钮”，并探测速度，保真度和能量耗散之间的梯度变化和权衡。它提供了一个直观的解释，最佳校对所需的条件，并揭示了意想不到的能力，变构分子击败霍普菲尔德限制的保真度，利用多样性的国家提供给他们。我们为活塞模型建立的框架也可以作为驱动生化系统的其他研究的基础。
英文摘要：
Kinetic proofreading is an error correction mechanism present in the processes of the central dogma and beyond, and typically requires the free energy of nucleotide hydrolysis for its operation. Though the molecular players of many biological proofreading schemes are known, our understanding of how energy consumption is managed to promote fidelity remains incomplete. In our work, we introduce an alternative conceptual scheme called 'the piston model of proofreading' where enzyme activation through hydrolysis is replaced with allosteric activation achieved through mechanical work performed by a piston on regulatory ligands. Inspired by Feynman's ratchet and pawl mechanism, we consider a mechanical engine designed to drive the piston actions powered by a lowering weight, whose function is analogous to that of ATP synthase in cells. Thanks to its mechanical design, the piston model allows us to tune the 'knobs' of the driving engine and probe the graded changes and trade-offs between speed, fidelity and energy dissipation. It provides an intuitive explanation of the conditions necessary for optimal proofreading and reveals the unexpected capability of allosteric molecules to beat the Hopfield limit of fidelity by leveraging the diversity of states available to them. The framework that we built for the piston model can also serve as a basis for additional studies of driven biochemical systems.
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