Emergence of scale-free distribution in protein-protein interaction networks based on random selection of interacting domain pairs

Biosystems. 2009 Feb;95(2):155-9. doi: 10.1016/j.biosystems.2008.10.002. Epub 2008 Nov 1.


Recent analyses of biological and artificial networks have revealed a common network architecture, called scale-free topology. The origin of the scale-free topology has been explained by using growth and preferential attachment mechanisms. In a cell, proteins are the most important carriers of function, and are composed of domains as elemental units responsible for the physical interaction between protein pairs. Here, we propose a model for protein-protein interaction networks that reveals the emergence of two possible topologies. We show that depending on the number of randomly selected interacting domain pairs, the connectivity distribution follows either a scale-free distribution, even in the absence of the preferential attachment, or a normal distribution. This new approach only requires an evolutionary model of proteins (nodes) but not for the interactions (edges). The edges are added by means of random interaction of domain pairs. As a result, this model offers a new mechanistic explanation for understanding complex networks with a direct biological interpretation because only protein structures and their functions evolved through genetic modifications of amino acid sequences. These findings are supported by numerical simulations as well as experimental data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Biological Evolution*
  • Computer Simulation
  • Models, Biological*
  • Protein Binding*
  • Protein Structure, Tertiary*
  • Proteins / metabolism*
  • Proteomics / methods*


  • Proteins