Background Currently a huge amount of protein-protein interaction data is available therefore extracting meaningful ones are a challenging task. In a protein-protein interaction network, hubs are considered as key proteins maintaining function and stability of the network. Therefore, studying protein-protein complexes from a structural perspective provides valuable information for predicted interactions. Results In this study, we have predicted by comparative modelling and docking methods protein-protein complexes of hubs of human NR-RTK network inferred from our earlier study. We found that some interactions are mutually excluded while others could occur simultaneously. This study revealed by structural analysis the key role played by Estrogen receptor (ESR1) in mediating the signal transduction between human Receptor Tyrosine kinases (RTKs) and nuclear receptors (NRs). Conclusions Although the methods require human intervention and judgment, they can identify the interactions that could occur together or ones that are mutually exclusive. This adds a fourth dimension to interaction network, that of time, and can assist in obtaining concrete predictions consistent with experiments. Open peer review This article was reviewed by Dr. Anthony Almudevar, Prof. James Faeder and Prof. Eugene Koonin. For the full reviews, please go to the Reviewers' comments.
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