Modeling the Two-Hybrid Detector: Experimental Bias on Protein Interaction Networks

This work was done to investigate the two-hybrid experiment for finding protein-protein interactions to explain the asymmetry found in the experimental data, and to help screen the data for high confidence interactions. By looking at the bait-prey experimental setup the resulting protein interaction network can be examined as a directed network (bait → prey). We have investigated two possible scenarios for the asymmetry in the directed network by developing a biochemical model for the protein-DNA and protein-protein bindings inside the living yeast. One scenario assumes a background activity of bait proteins acting even without the prey, the other scenario explores the asymmetry in the chemistry associated with the bait being automatically located in the right position on the DNA. We conclude that the latter model gives the best description of the observed asymmetry.