Thermodynamics and kinetics of an A-U RNA base pair under force studied by molecular dynamics simulations
Thermodynamics and kinetics of an A-U RNA base pair under force studied by molecular dynamics simulations
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DOI：
10.1103/physreve.107.024404
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发表时间：
2023-02-07
影响因子：
2.4
通讯作者：
Zhang，Wenbing
中科院分区：
文献类型：
--
作者：
Yu，Ting;Liu，Taigang;Zhang，Wenbing
机械力已被广泛用于研究RNA的折叠和去折叠。单碱基对的打开和闭合是RNA折叠和去折叠的基本步骤，也是一些重要生物活动的基本行为，理解力如何影响单碱基对的打开和闭合对于理解机械力作用下RNA折叠和去折叠的机制至关重要。在这项工作中，我们研究了机械力作用下的RNA碱基对的打开和关闭过程的恒力拉伸分子动力学模拟。研究发现，高机械力导致过度拉伸，并且打开状态是高能量状态。计算了碱基对开闭相变的焓变和熵变，在低作用力下的计算结果与最近邻模型的计算结果吻合较好。得到了开闭速率与温度和力的关系。确定了在机械力作用下碱基对开-关转变的过渡态位置。在没有力的情况下打开一个碱基对的自由能垒是焓增加，而从闭合状态到过渡状态的力所做的功降低了垒，增加了打开速率。在没有外力的情况下，碱基对闭合的自由能垒是由熵损失引起的，而外力从开放态到过渡态所作的功增加了自由能垒，降低了闭合速率。相变速率强烈地依赖于温度和力，而相变路径时间弱地依赖于力和温度。
Mechanical force has been widely used to study RNA folding and unfolding. Understanding how the force affects the opening and closing of a single base pair, which is a basic step for RNA folding and unfolding and a fundamental behavior in some important biological activities, is crucial to understanding the mechanism of RNA folding and unfolding under mechanical force. In this work, we investigated the opening and closing process of an RNA base pair under mechanical force with constant-force stretching molecular dynamics simulations. It was found that high mechanical force results in overstretching, and the open state is a high-energy state. The enthalpy and entropy change of the base-pair opening-closing transition were obtained and the results at low forces were in good agreement with the nearest-neighbor model. The temperature and force dependence of the opening and closing rates were also obtained. The position of the transition state for the base-pair opening-closing transition under mechanical force was determined. The free energy barrier of opening a base pair without force is the enthalpy increase, and the work done by the force from the closed state to the transition state decreases the barrier and increases the opening rate. The free energy barrier of closing the base pair without force results from the entropy loss, and the work done by the force from the open state to the transition state increases the barrier and decreases the closing rate. The transition rates are strongly dependent on the temperature and force, while the transition path times are weakly dependent on force and temperature.