加拿大蒙特利尔大学Alexis Vallée-Bélisle团队报道了化学通信动力学的编程——诱导契合与构象的选择。相关研究成果于2024年12月19日发表在《美国化学会杂志》。

地球上的生命依赖于化学通信和生物分子开关整合各种化学信号的能力，这些信号在微秒到几天的时间范围内触发其激活或失活。类似地编程和控制人工开关动力学的能力将极大地帮助未来化学和纳米技术系统的设计和优化。生物分子开关通常采用两种不同的结构转换机制：诱导配合（IF）和构象选择（CS）。尽管进行了60年的实验和理论研究，但这两种机制的动力学和进化优势仍不清楚。

该文中，研究人员创建了一个简单的模块化DNA开关，可以通过这两种机制运行，并且可以很容易地调整和适应其热力学和动力学参数。研究发现，当配体能够结合其无活性构象（IF）时，开关的激活速率最快。

相比之下，当配体只能结合开关（CS）的活性构象时，通过简单地调整其构象平衡，其激活速率可以很容易地编程到许多数量级。研究人员通过设计一种药物输送血管来证明这两种机制的编程能力，该血管可以编程以在不同的时间尺度（>1000倍）释放药物。

总体而言，研究结果提供了一种可编程的策略来优化分子系统和纳米机器的动力学，同时也说明了进化如何利用IF和CS机制来优化生物分子开关的动力学。

附：英文原文

Title: Programming the Kinetics of Chemical Communication: Induced Fit vs Conformational Selection

Author: Carl Prévost-Tremblay, Achille Vigneault, Dominic Lauzon, Alexis Vallée-Bélisle

Issue&Volume: December 19, 2024

Abstract: Life on Earth depends on chemical communication and the ability of biomolecular switches to integrate various chemical signals that trigger their activation or deactivation over time scales ranging from microseconds to days. The ability to similarly program and control the kinetics of artificial switches would greatly assist the design and optimization of future chemical and nanotechnological systems. Two distinct structure-switching mechanisms are typically employed by biomolecular switches: induced fit (IF) and conformational selection (CS). Despite 60 years of experimental and theoretical investigations, the kinetic and evolutive advantages of these two mechanisms remain unclear. Here, we have created a simple modular DNA switch that can operate through both mechanisms and be easily tuned and adapted to characterize its thermodynamic and kinetic parameters. We show that the fastest activation rate of a switch occurs when the ligand is able to bind its inactive conformation (IF). In contrast, we show that when the ligand can only bind the active conformation of the switch (CS), its activation rate can be easily programmed over many orders of magnitude by a simple tuning of its conformational equilibrium. We demonstrate the programming ability of both these mechanisms by designing a drug delivery vessel that can be programmed to release a drug over different time scales (>1000-fold). Overall, these findings provide a programmable strategy to optimize the kinetics of molecular systems and nanomachines while also illustrating how evolution may have taken advantage of IF and CS mechanisms to optimize the kinetics of biomolecular switches.

DOI: 10.1021/jacs.4c08597

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c08597