Regarding the TIR domain, Mahita and Sowdhamini investigated the effect of key mutations on the conformational dynamics, based on TLR2 and TLR3 102 . For that, they used a combination of MD simulations, protein-protein interaction and protein structure network analyses. They carried out the analyses for eight different complexes, including not only wild-type and mutant dimers, but also wild-type and mutant trimers (TIR dimers with different adaptor proteins). They highlighted the significant differences between the dimer interfaces of the wild type and mutant forms and also provided a possible explanation of how the introduced mutations may affect adaptor binding to the receptor. For the proline-to-histidine (P681H) mutation in the TIR domain of TLR2, they observed an increase in the stability of the TLR1-TLR2 heterodimer. This mutation also affected the surface of the putative adaptor-binding platform causing it to become slightly more curved. For the alanine-to-proline (A795P) mutation in the TIR domain of TLR3, they pointed out that individual subunits in a mutant tilt slightly more toward each other in comparison to the wild type. Such a subtle change may influence the orientation of the BB-loops (important for mediating interactions between dimer subunits) on the homodimer, and thus also the binding of the adaptor proteins -MyD88 and TRIF. The authors pointed out that the obtained results were based on the assumption that TLR2 and TLR3 TIR dimer adopt a similar conformation as that of the TLR10 TIR dimer crystal structure. As they admitted, this does not rule out the possibility of the dimers adopting a different TIR dimer conformation during signal transduction, e.g. an asymmetrical arrangement.