Modeling structural protein interaction networks for betweenness analysis

Abstract

Protein-protein interactions are usually represented as interaction networks (graphs), where the proteins are represented as nodes and the connections between the interacting proteins are shown as edges. Proteins or interactions with high betweenness are considered as key connector members of the network. The interactions of a protein are dictated by its structure. In this study, we propose a new protein interaction network model taking structures of proteins into consideration. With this model, it is possible to reveal simultaneous and mutually exclusive interactions of a protein. Effect of mutually exclusive interactions on information flow in a network is studied with weighted edge betweenness analysis and it is observed that a total of 68% of bottlenecks found in p53 pathway network differed from bottlenecks found via regular edge betweenness analysis. The new network model favored the proteins which have regulatory roles and take part in cell cycle and molecular functions like protein binding, transcription factor binding, and kinase activity.