FREE ENERGY CONVERSION IN BIOLOGY

生物学中的自由能量转换

• 批准号: 6105211
• 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/6105211
• 关键词: active transport; bioenergetics; biophysics; catalyst; chemical models; electric field; enzyme activity; hydrolysis; kinesin; microtubules; thermodynamics

Two topics related to the general field of free energy conversion in biology have been studied and gained great progress. First, we continued our study of the general dynamic properties of a Brownian particle in a fluctuating periodic potential. We have obtained a general formalism for this Brownian motion system, which can be used to calculate the velocity of the movement of a large bead on a periodic biopolymer (such as a microtubule) powered by a one-headed motor molecule (such as kinesin), as measured in in vitro experiments. The formalism can also be used to design or set up devices for the separation of proteins or small particles based their sizes and charges, etc.. Specifically, we have found that charged particles with different charges or different diffusion coefficients can be made to move in opposite directions in a fluctuating linear periodic potential. Thus, particle separation should be more efficient based on this principle than on other conventional methods, such as the electrophoresis. The second topic is related to the regulation of muscle contraction (the mechano-chemical free energy conversion system). Specifically, we were interested in the question of how the regulatory protein, caldesmon, found on smooth muscles controls the generation of the force between the myosin head (the cross-bridge)and the actin, responsible for muscle contraction. In general, caldesmon molecules can reduce the force generation by reducing the ATP hydrolysis rate or by reducing the number of binding sites on actin for myosin heads. Using equilibrium binding data measured for the simultaneous binding of myosin and caldesmon molecules to actin, we have concluded that there are at least two modes of simultaneous binding of myosin and caldesmon to actin: the pure competitive and the mosaic multiple binding. In this study, we have developed a kinetic Monte Carlo method to differentiate this two binding models. When applied to the kinetic data measured by Dr. Chalovich and his colleagues (at University of East North Carolina), we have found that the binding of myosin and caldesmon to actins without tropomyosin is more like pure competitive. On the other hand, the binding to actins with tropomyosins (a condition in real muscle) can be fitted with both models. The method can be extended to binding models involving more than two ligands and should be useful in delineating different modes of regulation of different regulatory proteins in a complex system (e.g., such as in a protein transcription complex).

与自由能一般领域有关的两个问题 生物转化的研究取得了很大进展。 首先，我们继续我们的研究一般动态特性的一个 涨落周期势场中的布朗粒子。我们有 得到了这个布朗运动系统的一般形式， 它可以用来计算运动的速度， 周期性生物聚合物（如微管）上的大珠 由单头马达分子（如驱动蛋白）提供动力， 在体外实验中测量。形式主义也可以用来 设计或建立用于分离蛋白质或小分子的装置， 粒子基于它们的大小和电荷等。具体来说，我们有 发现带有不同电荷的带电粒子 可以使扩散系数沿相反方向移动， 波动的线性周期电位。因此，颗粒分离 基于这一原则，应该比基于其他原则更有效率。 常规方法，如电泳。第二 主题与肌肉收缩的调节有关（ 机械-化学自由能转换系统）。我们特别 对调节蛋白如何 钙调素，发现在平滑肌控制的产生， 肌球蛋白头（横桥）和肌动蛋白之间的力， 负责肌肉收缩。一般来说，钙调素分子 可以通过减少ATP水解来减少力的产生， 速率或通过减少肌动蛋白上肌球蛋白结合位点的数量 构造标准部件.使用测定的 肌球蛋白和钙调素分子与肌动蛋白的同时结合， 我们得出结论，至少有两种模式， 肌球蛋白和钙调蛋白与肌动蛋白的同时结合：纯的 竞争性和嵌合多重结合。本研究通过 开发了一种动力学蒙特卡罗方法来区分这两个 绑定模型当应用于由Dr. Chalovich和他的同事（在东北大学） 卡罗莱纳），我们发现肌球蛋白和钙调素的结合 与没有原肌球蛋白的肌动蛋白相比更像是纯粹的竞争。上 另一方面，肌动蛋白与原肌球蛋白的结合（ 真实的肌肉）可以与这两种模型配合。该方法可 扩展到涉及两个以上配体的结合模型， 应有助于界定不同的监管模式， 复杂系统中的不同调节蛋白（例如，诸如以 蛋白质转录复合物）。