Guided example 3 – building a structural model based on sequence similarity

Homology modelling is the process of estimating a theoretical structure of a protein by building a structural template from homologous sequences and threading your sequence to this template and optimising it.

Scenario

Jan is interested in interleukin 1-receptor-associated kinases (IRAKs) as possible targets for cancer therapy. Several mutations in IRAK2 are associated with cancers, so Jan would like to investigate IRAK2 as a possible new target. There are quite a few small-molecule inhibitors available for related proteins and Jan wants to know whether they’d be likely to bind to IRAK2. However, there is no crystal structure available for the kinase domain of IRAK2, so Jan wants to model the structure to see whether it’s likely to resemble the 3D structures of other IRAKs.