Internal coarse-graining of molecular systems
Internal coarse-graining of molecular systems
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DOI：
10.1073/pnas.0809908106
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发表时间：
2009-04-21
影响因子：
11.1
通讯作者：
Fontana, Walter
中科院分区：
文献类型：
--
作者：
Feret, Jerome;Danos, Vincent;Fontana, Walter
分子信号网络的建模者必须科普由翻译后修饰和复合物形成产生的蛋白质状态的组合爆炸。基于规则的模型提供了一个强大的替代方法，需要显式枚举系统的所有可能的分子物种。这些模型由规定特定蛋白质-蛋白质相互作用发生的（部分）上下文的正式规则组成。这些上下文指定的分子模式通常不如分子种类详细。然而，执行基于规则的动态需要随机模拟，这可能是非常昂贵的。因此，它似乎是可取的，以转换为一个减少系统的微分方程的规则指定的相互作用，通过利用粒度为基础的模型。我们提出了一个正式的（和自动化）的方法，用于构建一个粗粒度和自洽的动力系统，旨在分子模式，可区分的原系统的动力学假设的规则。该方法在形式上是合理的，并且从不需要执行基于规则的模型。粗粒度的变量不依赖于规则中出现的速率常数的值，并且通常形成可以服从于数值积分和进一步的模型简化技术的大大降低的维度的系统。
Modelers of molecular signaling networks must cope with the combinatorial explosion of protein states generated by posttranslational modifications and complex formation. Rule-based models provide a powerful alternative to approaches that require explicit enumeration of all possible molecular species of a system. Such models consist of formal rules stipulating the (partial) contexts wherein specific protein-protein interactions occur. These contexts specify molecular patterns that are usually less detailed than molecular species. Yet, the execution of rule-based dynamics requires stochastic simulation, which can be very costly. It thus appears desirable to convert a rule-based model into a reduced system of differential equations by exploiting the granularity at which rules specify interactions. We present a formal (and automated) method for constructing a coarse-grained and self-consistent dynamical system aimed at molecular patterns that are distinguishable by the dynamics of the original system as posited by the rules. The method is formally sound and never requires the execution of the rule-based model. The coarse-grained variables do not depend on the values of the rate constants appearing in the rules, and typically form a system of greatly reduced dimension that can be amenable to numerical integration and further model reduction techniques.