Kinetic Simulations of Minimal Living Systems

最小生命系统的动力学模拟

基本信息

批准号：
6526127
负责人：
PAUL A. LINDAHL
金额：
$ 10.91万
依托单位：
TEXAS A&M UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-08-01 至 2004-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6526127
关键词：
Mycoplasma cell biology computer simulation mathematical model method development model design /development molecular assembly /self assembly molecular biology organism

项目摘要

DESCRIPTION (provided by the applicant): Given the information explosion accruing among the biological sciences, it is likely that, within a decade, the composition of simple living systems and the functions of every gene/protein contained therein will be understood. At that point, it may be possible, for the first time, to understand the property of life on a molecular level. Anticipating this, the goal of this proposal is to develop a methodology that uses this information to simulate the kinetics of minimal living systems at the molecular level (part I) and to apply this methodology to simulate the simplest organism, Mycoplasma genitalium (part II). The methodology will be developed using Mechanical Cells, simple hypothetical self-replicating systems with properties analogous to those of real cells. The methodology involves decomposing such systems into hierarchically organized structures and functions. These will be reorganized into mechanistic modules, collections of elementary chemical reactions (explicating the mechanism of the module) and the associated molecular components. Complete sets of modules must be autocatalytic, a required property of living systems. The ordinary differential equations corresponding to this reaction set will be generated and solved numerically. This will require simplifying and/or subdividing the system, solving the simpler system than linking. The resulting set of rate constants and copy numbers will be used in conjunction with a stochastic computer simulator to generate kinetic plots of each molecular component. The output of the simulations will be animated using 3D visualization software. Simulation and animations will be critically compared to the properties of real cells. Mechanism will be modified, corrected, and embellished as deficiencies are noted and more experimental data become available.

描述（申请人提供）：给定信息爆炸在生物科学中累积，在十年之内简单生活系统的组成和每个基因/蛋白质的功能其中包含将被理解。到那时，可能是可能的第一次，以分子水平了解生命的特性。预见到这一点，该提议的目标是开发一种方法论使用此信息模拟最小生活系统的动力学分子水平（第I部分），并应用此方法来模拟最简单的生物体，支原体生殖器（第二部分）。该方法将开发使用机械单元，简单假设的自我复制系统与类似于真实细胞的性质。该方法涉及将这种系统分解为层次组织的结构和功能。这些将被重组为机械模块，集合基本化学反应（解释模块的机制）和相关的分子成分。完整的模块必须是自催化，这是生活系统的必需属性。普通的差异将生成与此反应集的方程式数值。这将需要简化和/或细分系统，求解比链接更简单的系统。由此产生的速率常数和拷贝数将与随机计算机一起使用模拟器生成每个分子成分的动力图。输出模拟将使用3D可视化软件进行动画。模拟动画将与真实细胞的特性进行严格的比较。由于缺陷为注意到并提供更多的实验数据。