Mechanochemical Energy Transduction in Protein Motors

王0077971 ATP（腺苷三磷酸）是所有活细胞中普遍存在的化学能量分子。 ATP驱动的蛋白质马达在许多细胞功能中起核心作用。 例如，在有丝分裂过程中，驱动蛋白驱动胞内囊泡运输并移动染色体;肌球蛋白驱动肌肉收缩，V-ATP酶调节细胞内酸度。 理解ATP驱动马达的工作原理对于理解细胞内蛋白质转运和细胞运动至关重要。结构研究提供了马达蛋白的原子细节，并揭示了更多与它们催化的化学反应相关的构象变化信息。 目前的实验技术允许以皮牛顿的精度测量单个蛋白质马达的力，以纳米的分辨率测量运动。 这些进展，沿着数学模型和计算机处理能力的进步，使得对分子马达中机械力化学能量转换的探索变得前所未有的细致。 在这个项目中，研究者和他的同事们继续研究在F1 ATP酶以前的研究中出现的数学和物理问题。 这些问题涉及到蛋白质马达应该如何建模的分子细节，以及什么样的数学公式足以建模它们。 特别是，研究的重点是在ATP水解循环的催化位点的力产生的mechanismof。 这个关键过程的解决将阐明ATP驱动马达的工作原理，也可能阐明其他蛋白质马达的工作原理。 为了适应更复杂的建模，研究者开发了分析蛋白质结构和求解复杂模型方程的方法。 这些研究的结果为肌球蛋白和驱动蛋白二聚体的机械化学能量传递建模奠定了基础。 该方法是建模的连续随机运动的电机usingstochastic微分方程和耦合这些化学反应所描述的离散马尔可夫过程。 模型方程由基本的物理原理、结构数据、生物化学和生物物理测量数据构成，然后对这些方程进行数值分析。 希望这将导致ATP驱动电机的统一观点。 为了促进快速发展的生物技术领域，有必要从实验结果中推导出生物系统的简明机制。 这就需要应用数学和物理学的基本原理。 这个跨学科项目的目的是研究蛋白质利用化学能产生机械力的机制。 反过来，这些力量驱动着生命所必需的各种细胞过程。 在所有活细胞中，通用的化学能分子是ATP（三磷酸腺苷）。 ATP是利用从食物中提取的能量产生的，每个细胞的生命都依赖于ATP提供动力的过程。 例如，肌肉收缩是由ATP蛋白运动肌球蛋白直接驱动的。 因此，理解ATP蛋白马达的工作原理对于理解细胞的生命至关重要。

Wang0077971 ATP (adenosine triphosphate) is the universal chemicalenergy molecule in all living cells. ATP driven protein motorsplay a central role in many cell functions. For example, kinesindrives intracellular vesicle transportation and moves chromosomesduring mitosis; myosin drives muscle contraction, and theV-ATPases regulate intracellular acidity. Understanding theoperating principles of the ATP driven motors is crucial tocomprehending intracellular protein transport and cell motility.Structural studies are providing the atomic details of motorproteins, and are revealing more information about theconformational changes associated with the chemical reactionsthey catalyze. Current experimental technologies permit measuringforces of a single protein motor with piconewton precision andmotions with nanometer resolution. These advances, along withadvances in mathematical modeling and computer power, make itpossible to explore the mechanochemical energy transduction inmolecular motors in unprecedented detail. In this project, theinvestigator and colleagues pursue the mathematical and physicalissues that arose in the previous studies of F1 ATPase. Theseconcern the molecular details of how protein motors should bemodeled and what mathematical formulations are adequate formodeling them. In particular, the study focuses on the mechanismof force generation at the catalytic site during the ATPhydrolysis cycle. Resolution of this key process will illuminatethe operating principles of this ATP driven motor, and likelyother protein motors as well. To accommodate more sophisticatedmodeling, the investigator develops methods for analyzing proteinstructures and solving complex model equations. The results ofthese studies set the stage for modeling the mechanochemicalenergy transduction in myosin and kinesin dimers. The approach isto model the continuous stochastic motion of the motor usingstochastic differential equations and couple these to thechemical reactions described by discrete Markov processes. Themodel equations are constructed from basic physical principles,structural data, and biochemical and biophysical measurements.These equations are then analyzed numerically. The hope is thatthis will lead to a unified view of ATP driven motors. To facilitate the fast growing field of biotechnology, it isnecessary to deduce concise mechanisms for biological systemsfrom experimental results. This requires the application offundamental principles from the mathematical and physicalsciences. The purpose of this interdisciplinary project is tostudy the mechanisms by which proteins use chemical energy togenerate mechanical forces. In turn, these forces drive a widevariety of cellular processes essential to life. In all livingcells, the universal chemical energy molecule is ATP (adenosinetriphosphate). ATP is produced using the energy extracted fromfood, and the life of every cell depends on processes that arepowered by ATP. For example, muscle contraction is directlydriven by the ATP protein motor myosin. Therefore, understandingthe operating principles of the ATP protein motors is central tocomprehending the life of cells.