Toll-like receptors are activated by interactions between TIR domeins. Homology models are built for the TIR domains. The MAPPIT method and in vitro binding studies with recombinant TIR domains are combined with extensive mutagenesis studies to identify the interaction interfaces. These data are used as input for data-driven in silico docking. This leads to experimentally validated models for TIR-TIR complexes.