肌球蛋白V持续运动特性的动力学研究

发布时间：2018-04-24 13:17

本文选题：肌球蛋白V + 持续性运动　；参考：《内蒙古大学》2017年博士论文

【摘要】：肌球蛋白V作为最常见的线性分子马达之一,是将ATP水解过程中释放的化学能转化为机械功的纳米机器,参与细胞器和mRNA等的输运过程,其沿着肌动蛋白丝所作的定向和持续运动,是实现这些功能的基本条件。驻留时间、平均速度及运行长度是反映肌球蛋白V持续运动特性的重要参数。近年来的单分子实验结果表明,肌球蛋白V驻留时间的分布呈双指数曲线的形式,指数的系数与ATP和ADP的浓度及负载的大小密切相关,而平均速度与运行长度的分布也同样受到ATP和ADP的浓度及负载的影响。现有的理论研究尚难以完整地解释上述实验现象。肌球蛋白V的运动蕴含着深刻的化学动力学机制,因此建立力学化学动力学模型,是研究其运动特性的有效方法。基于以下实验结果:ATP浓度越高,肌球蛋白持续运动的驻留时间越短,平均速度越大;ADP的释放限制肌球蛋白力学化学循环速率,本文将ADP的释放及其逆过程和ATP与肌球蛋白V的结合这两个因素,作为决定肌球蛋白V运动特性的主要矛盾,对传统的多态模型进行了简化,建立了一种三态力学化学耦合模型。相对于传统的力学化学耦合模型,本模型在以下三个方面做了简化:(1)从统计意义上,认为肌球蛋白两个头部的力学和化学循环相对独立,从而在计算中只需考虑单头的循环过程;(2)将肌球蛋白V的化学循环过程,,简化为肌球蛋白V结合ATP、结合ADP和释放ADP几个步骤,忽略了 Pi的释放等细节。(3)在力学和化学耦合机制方面,不考虑肌球蛋白运动过程中复杂的构象变化及构象变化对双头化学反应速率的影响,仅考虑负载对化学反应速率的影响。相比之下,传统的多态模型考虑了较多的状态转化及力学化学耦合过程,虽然能够计算出更为精确的结果,但难以给出分子马达持续运动参数的解析解。与最简单的二态模型相比,本文的三态模型能够将ATP水解循环中ATP与ADP所起的作用区分开,从而能体现ATP与ADP对分子马达持续运动特性的影响,弥补二态模型的不足。依据简化的三态力学化学模型,采用化学动力学方法,本文定量研究了肌球蛋白V的持续运动特性,重点考察ATP与ADP的浓度以及负载对驻留时间、平均速度以及运行长度的影响,得到以下结果:(1)得出了驻留时间分布的双指数解析解和平均速度的数学表达式,明确了它们与ATP浓度、ADP浓度以及负载的定量关系;(2)通过肌球蛋白V双头驻留时间的联合概率分布,得出了运行长度分布的解析解。理论计算的结果与实验数据基本一致,证明本文提出的简化模型合理可行,为研究肌球蛋白V提供了新的理论工具。本文的研究还发现,ATP和ADP的浓度比对于驻留时间、平均速度的值具有决定性的作用,ATP和ADP之间的竞争是决定肌球蛋白V的运动特性的重要因素。
[Abstract]:Myosin V, as one of the most common linear molecular motors, is a nano machine that transforms the chemical energy released into mechanical work during the hydrolysis of ATP, and participates in the transport process of the organelles and mRNA. The orientation and continuous movement along the actin filaments is the basic condition for the realization of these work energy. The residence time, average speed and operation are the basic conditions. The length is an important parameter to reflect the continuous motion characteristics of myosin V. In recent years, the results of single molecular experiments show that the distribution of myosin V residing time is in the form of a double exponential curve, the index coefficient is closely related to the concentration of ATP and ADP and the size of the load, and the distribution of average velocity and operation length is also similar to that of ATP and ADP. The influence of concentration and load. The existing theoretical study is still difficult to fully explain the above experimental phenomena. The movement of myosin V contains a profound chemical kinetic mechanism. Therefore, the establishment of a mechanical chemical kinetic model is an effective method to study the motion characteristics of myosin. Based on the results of the following experimental results, the higher the concentration of ATP, the continuous movement of myosin The shorter the retention time, the greater the average speed; the release of ADP limits the mechanochemical cycle rate of myosin. In this paper, the release of ADP and its inverse process, and the combination of ATP and myosin V, are the main contradictions to determine the kinetic characteristics of myosin V, and the traditional multi state model is simplified, and a mechanization of the mechanization of the myosin V is established. Compared with the traditional mechanical and chemical coupling model, this model has been simplified in three aspects: (1) in statistical sense, the mechanical and chemical cycles of myosin two heads are relatively independent, so that only the cycle process of single head should be considered in the calculation; (2) the chemical cycle of myosin V is simplified as the muscle. Globulin V combined with ATP, combined with ADP and release of ADP, neglecting the details of Pi release. (3) in the mechanical and chemical coupling mechanism, the effect of complex conformation changes and conformation changes on the rate of chemical reaction in the process of myosin movement is not considered, only considering the effect of load on the chemical reaction rate. Compared with the simplest two state model, the three state model in this paper can separate the action of ATP from ADP in the ATP hydrolysis cycle, so that the model can be used as a result. The effect of ATP and ADP on the continuous motion characteristics of the molecular motor is reflected, and the deficiency of the two state model is made up. Based on the simplified three state mechanical chemical model, the continuous motion characteristics of myosin V are studied by chemical kinetics method. The concentration of ATP and ADP and the standing time, average speed and operation length of the load on the residence time are emphatically investigated. The following results are obtained: (1) the mathematical expressions of the two exponential analytic solutions and the average velocity of the residing time distribution are obtained, and the quantitative relation between them and the concentration of ATP, ADP concentration and the load is clarified. (2) the analytical solution of the operation length distribution is obtained through the joint probability distribution of the myosin V double head standing time. The results show that the simplified model proposed in this paper is reasonable and feasible, which provides a new theoretical tool for the study of myosin V. The study also found that the concentration of ATP and ADP has a decisive effect on the value of the residing time and the mean velocity, and the competition between ATP and ADP is the determination of the motion characteristics of myosin V. Important factors.

【学位授予单位】：内蒙古大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：Q51

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