Sorokina Oksana, Sorokin Anatoly, Armstrong J Douglas
School of Informatics, University of Edinburgh, Edinburgh, UK.
Mol Biosyst. 2011 Oct;7(10):2813-23. doi: 10.1039/c1mb05152k. Epub 2011 Aug 26.
The postsynaptic compartment of the excitatory glutamatergic synapse contains hundreds of distinct polypeptides with a wide range of functions (signalling, trafficking, cell-adhesion, etc.). Structural dynamics in the post-synaptic density (PSD) are believed to underpin cognitive processes. Although functionally and morphologically diverse, PSD proteins are generally enriched with specific domains, which precisely define the mode of clustering essential for signal processing. We applied a stochastic calculus of domain binding provided by a rule-based modelling approach to formalise the highly combinatorial signalling pathway in the PSD and perform the numerical analysis of the relative distribution of protein complexes and their sizes. We specified the combinatorics of protein interactions in the PSD by rules, taking into account protein domain structure, specific domain affinity and relative protein availability. With this model we interrogated the critical conditions for the protein aggregation into large complexes and distribution of both size and composition. The presented approach extends existing qualitative protein-protein interaction maps by considering the quantitative information for stoichiometry and binding properties for the elements of the network. This results in a more realistic view of the postsynaptic proteome at the molecular level.
兴奋性谷氨酸能突触的突触后区室包含数百种具有广泛功能（信号传导、运输、细胞粘附等）的不同多肽。突触后致密区（PSD）的结构动力学被认为是认知过程的基础。尽管PSD蛋白在功能和形态上具有多样性，但它们通常富含特定结构域，这些结构域精确地定义了信号处理所必需的聚集模式。我们应用基于规则的建模方法提供的结构域结合随机演算，将PSD中高度组合的信号通路形式化，并对蛋白质复合物的相对分布及其大小进行数值分析。我们通过规则指定了PSD中蛋白质相互作用的组合方式，同时考虑了蛋白质结构域结构、特定结构域亲和力和相对蛋白质可用性。利用这个模型，我们探究了蛋白质聚集成大复合物的关键条件以及大小和组成的分布情况。所提出的方法通过考虑网络元素的化学计量和结合特性的定量信息，扩展了现有的定性蛋白质-蛋白质相互作用图谱。这使得在分子水平上对突触后蛋白质组有了更现实的认识。
