Kinetic Simulations of Minimal Living Systems

描述(由申请人提供)：鉴于信息爆炸 在生物科学中积累起来的，很可能在十年内， 简单生命系统的组成和每个基因/蛋白质的功能 其中所包含的内容将被理解。在这一点上，也许有可能， 第一次，在分子水平上了解生命的性质。 考虑到这一点，本提案的目标是开发一种 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 生殖支原体(第二部分)。方法论将被开发出来 使用机械细胞，简单的假设自我复制系统 性质类似于真实细胞的性质。方法论包括 将这样的系统分解成分层组织的结构 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 自我催化，生命系统的必备特性。常微分仪 将生成并求解与此反应集相对应的方程 从数字上讲。这将需要简化和/或细分系统， 解决比链接更简单的系统。得到的一组速率常量 复制数将与随机计算机结合使用 模拟器，用于生成每个分子组分的动力学曲线图。的产出 模拟将使用3D可视化软件进行动画制作。模拟法 动画将被关键地与真实细胞的属性进行比较。 机制将根据缺陷进行修改、纠正和润色 注意到，并且有更多的实验数据可用。

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.