discovering domains mediating protein interactions

background: protein-protein interactions do not provide any direct information re­garding the domains within the proteins that mediate the interactions. the majority of proteins are multi domain proteins and the interaction between them is often defined by the pairs of their domains. most of the former studies focus only on interacting do­main pairs. however they do not consider the interactions that require the presence of a third domain. objectives: in this manuscript, we define the concept of necessary and sufficient triplets of domains and mediator domain. materials and methods: we approximate these conditions by pragmatic statistical defi­nitions on a set of gold-standard interacting protein pairs and a set of gold-standard non-interacting protein pairs. results: in this paper we introduce a new method for the prediction of the interaction between two domains using third domains as a mediator.we show that the mediator domain has an effective role in the interaction between proteins. conclusions: by using these concepts, we introduce a method for the prediction of the interaction between two domains. subsequently by evaluating the performance of our method on the yeast protein interactions data set, we show that the mediator domain has an effective role in the interaction between proteins.