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（由申请人提供）：考虑到信息爆炸随着生物科学领域的不断积累，十年之内，简单生命系统的组成以及每个基因/蛋白质的功能其中包含的内容将被理解。到那时，也许有可能，对于第一次，在分子水平上了解生命的属性。预见到这一点，本提案的目标是开发一种方法，使用这些信息来模拟最小生命系统的动力学分子水平（第一部分）并应用这种方法来模拟最简单的有机体，生殖支原体（第二部分）。将制定方法论使用机械细胞，简单的假设自我复制系统与真实细胞类似的特性。该方法论涉及将此类系统分解为分层组织的结构功能。这些将被重新组织成机械模块、集合基本化学反应（解释模块的机理）和相关的分子成分。成套模块必须是自催化，生命系统所需的特性。普通差速器将生成并求解与该反应组相对应的方程数字上。这将需要简化和/或细分系统，解决比链接更简单的系统。所得的速率常数集和拷贝数将与随机计算机结合使用模拟器生成每个分子成分的动力学图。的输出模拟将使用 3D 可视化软件进行动画处理。模拟动画将与真实细胞的属性进行严格的比较。机制将根据缺陷进行修改、纠正和完善注意到并且可以获得更多的实验数据。