Colvin Joshua, Monine Michael I, Faeder James R, Hlavacek William S, Von Hoff Daniel D, Posner Richard G
Computational Biology Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
Bioinformatics. 2009 Apr 1;25(7):910-7. doi: 10.1093/bioinformatics/btp066. Epub 2009 Feb 11.
Interactions of molecules, such as signaling proteins, with multiple binding sites and/or multiple sites of post-translational covalent modification can be modeled using reaction rules. Rules comprehensively, but implicitly, define the individual chemical species and reactions that molecular interactions can potentially generate. Although rules can be automatically processed to define a biochemical reaction network, the network implied by a set of rules is often too large to generate completely or to simulate using conventional procedures. To address this problem, we present DYNSTOC, a general-purpose tool for simulating rule-based models.
DYNSTOC implements a null-event algorithm for simulating chemical reactions in a homogenous reaction compartment. The simulation method does not require that a reaction network be specified explicitly in advance, but rather takes advantage of the availability of the reaction rules in a rule-based specification of a network to determine if a randomly selected set of molecular components participates in a reaction during a time step. DYNSTOC reads reaction rules written in the BioNetGen language which is useful for modeling protein-protein interactions involved in signal transduction. The method of DYNSTOC is closely related to that of StochSim. DYNSTOC differs from StochSim by allowing for model specification in terms of BNGL, which extends the range of protein complexes that can be considered in a model. DYNSTOC enables the simulation of rule-based models that cannot be simulated by conventional methods. We demonstrate the ability of DYNSTOC to simulate models accounting for multisite phosphorylation and multivalent binding processes that are characterized by large numbers of reactions.
DYNSTOC is free for non-commercial use. The C source code, supporting documentation and example input files are available at http://public.tgen.org/dynstoc/.
Supplementary data are available at Bioinformatics online.
分子间的相互作用，如具有多个结合位点和/或多个翻译后共价修饰位点的信号蛋白，可以使用反应规则进行建模。规则全面但隐含地定义了分子相互作用可能产生的单个化学物种和反应。虽然规则可以自动处理以定义生化反应网络，但一组规则所隐含的网络通常太大，无法完全生成或使用传统程序进行模拟。为了解决这个问题，我们提出了DYNSTOC，一种用于模拟基于规则模型的通用工具。
DYNSTOC实现了一种空事件算法，用于模拟均匀反应隔室内的化学反应。该模拟方法不需要预先明确指定反应网络，而是利用基于规则的网络规范中的反应规则来确定在一个时间步长内随机选择的一组分子成分是否参与反应。DYNSTOC读取用BioNetGen语言编写的反应规则，这对于模拟信号转导中涉及的蛋白质-蛋白质相互作用很有用。DYNSTOC的方法与StochSim的方法密切相关。DYNSTOC与StochSim的不同之处在于允许根据BNGL进行模型规范，这扩展了模型中可以考虑的蛋白质复合物的范围。DYNSTOC能够模拟传统方法无法模拟的基于规则的模型。我们展示了DYNSTOC模拟考虑多位点磷酸化和多价结合过程的模型的能力，这些过程具有大量反应的特征。
DYNSTOC可免费用于非商业用途。C源代码、支持文档和示例输入文件可在http://public.tgen.org/dynstoc/获取。
补充数据可在《生物信息学》在线获取。
