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Modeling and simulating networks of interdependent protein interactions

Abstract

Protein interactions are fundamental building blocks of biochemical reaction systems underlying cellular functions. The complexity and functionality of these systems emerge not only from the protein interactions themselves but also from the dependencies between these interactions, as generated by allosteric effects or mutual exclusion due to steric hindrance. Therefore, formal models for integrating and utilizing information about interaction dependencies are of high interest. Here, we describe an approach for endowing protein networks with interaction dependencies using propositional logic, thereby obtaining constrained protein interaction networks ("constrained networks''). The construction of these networks is based on public interaction databases as well as text-mined information about interaction dependencies. We present an efficient data structure and algorithm to simulate protein complex formation in constrained networks. The efficiency of the model allows fast simulation and facilitates the analysis of many proteins in large networks. In addition, this approach enables the simulation of perturbation effects, such as knockout of single or multiple proteins and changes of protein concentrations. We illustrate how our model can be used to analyze a constrained human adhesome protein network, which is responsible for the formation of diverse and dynamic cell-matrix adhesion sites. By comparing protein complex formation under known interaction dependencies versus without dependencies, we investigate how these dependencies shape the resulting repertoire of protein complexes. Furthermore, our model enables investigating how the interplay of network topology with interaction dependencies influences the propagation of perturbation effects across a large biochemical system. Our simulation software CPINSim (for Constrained Protein Interaction Network Simulator) is available under the MIT license at http://github.com/BiancaStoecker/cpinsim and as a Bioconda package (https://bioconda.github.io).

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Publication details

The article was received on 22 Jan 2018, accepted on 07 Apr 2018 and first published on 11 Apr 2018


Article type: Paper
DOI: 10.1039/C8IB00012C
Citation: Integr. Biol., 2018, Accepted Manuscript
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    Modeling and simulating networks of interdependent protein interactions

    B. K. Stöcker, J. Köster, E. Zamir and S. Rahmann, Integr. Biol., 2018, Accepted Manuscript , DOI: 10.1039/C8IB00012C

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