Perturbation waves in proteins and protein networks: applications of percolation and game theories in signaling and drug design.

The network paradigm is increasingly used to describe the dynamics of complex systems. Here we review the current results and propose future development areas in the assessment of perturbation waves, i.e. propagating structural changes in amino acid networks building individual protein molecules and in protein-protein interaction networks (interactomes). We assess the possibilities and critically review the initial attempts for the application of game theory to the often rather complicated process, when two protein molecules approach each other, mutually adjust their conformations via multiple communication steps and finally, bind to each other. We also summarize available data on the application of percolation theory for the prediction of amino acid network- and interactome-dynamics. Furthermore, we give an overview of the dissection of signals and noise in the cellular context of various perturbations. Finally, we propose possible applications of the reviewed methodologies in drug design.