FREE ENERGY CONVERSION IN BIOLOGY

生物学中的自由能量转换

• 批准号: 2572983
• 负责人: Yin-Ching Iris Chen
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2572983
• 关键词: active transport; bioenergetics; biophysics; catalyst; chemical models; electric field; enzyme activity; hydrolysis; kinesin; microtubules; thermodynamics

Single kinesin molecules (a motor protein) have been shown to be able to move unidirectionally on a microtubule (a periodic biopolymer made of identical monomer subunits) by catalyzing the hydrolysis of ATP. Exactly how the chemical free energy of ATP hydrolysis is converted into mechanical energy in this system is not clear. In the last report, we showed that an enzymatic Brownian particle can be driven to move unidirectionally on a static periodic electric potential field by the free energy of the chemical reaction it catalyzes, if at least one of the intermediates of the catalytic cycle is charged and the potential field in each period is not symmetrical. This is the first model with explicit mechanisms showing how chemical-mechanical free energy transduction is carried out. This year, we have extended the research further and concentrated our work on two problems. First, we examined how the Brownian particle behave when the enzymatic reactions of the particle contains more than one cycle and more than one charged states. It was found that the direction of the particle movement depended not only on the asymmetry of the potential, but also on the detailed mechanisms of the catalytic reactions. This result suggests an experimental separation method for protein molecules based on their enzymatic activities. Second, the formalism and the calculation procedure have been extended and reformulated so that they become applicable to kinesin molecules. In general, the existence of a static periodic electric field near the surface of a microtubule is not very likely. Therefore, the model based on direct interaction between charged states and a periodic asymmetric electric field may not be directly applicable to the kinesin system. Instead, we have used the same "cross-bridge" concept as in muscle contraction, where force is generated by attaching a part of the kinesin (the cross- bridge) to a specific binding site on each monomer of the microtubule. The formalism is currently used in assessing the mechanisms of kinesin movement based on in vitro experimental data.

单个驱动蛋白分子（一种运动蛋白）已被证明能够 在微管（一种周期性生物聚合物）上单向移动 相同的单体亚基）通过催化 ATP 水解。 ATP 水解的化学自由能到底是如何转化的 在这个系统中转化为机械能尚不清楚。 在最后 报告中，我们表明酶促布朗粒子可以被驱动 在静态周期性电势场上单向移动 它催化的化学反应的自由能，如果至少一个 催化循环的中间体被充电并且 每个周期的势场不对称。 这是第一个 具有明确机制的模型显示了化学机械如何自由 进行能量转换。 今年，我们延长了 进一步研究并将我们的工作集中在两个问题上。 首先，我们 研究了酶促反应时布朗粒子的行为 粒子包含一个以上的循环和一个以上的带电 州。 结果发现，粒子运动方向 不仅取决于势能的不对称性，还取决于 催化反应的详细机制。 这一结果表明 一种基于蛋白质分子的实验分离方法 酶活性。 二、形式主义与计算 程序已被扩展和重新制定，以便它们成为 适用于驱动蛋白分子。 一般来说，存在一个 微管表面附近的静态周期性电场为 不太可能。 因此，基于直接交互的模型 带电状态和周期性不对称电场之间可以 不能直接应用于驱动蛋白系统。 相反，我们有 使用与肌肉收缩相同的“跨桥”概念，其中 力是通过连接驱动蛋白的一部分（交叉 桥）到微管每个单体上的特定结合位点。 该形式目前用于评估驱动蛋白的机制 基于体外实验数据的运动。