The human epidermal growth factor receptor 2 (HER2) is over-expressed in a significant proportion of breast cancers and is a target for therapeutic intervention with monoclonal antibodies and small molecule inhibitors. The class of novel binding proteins Designed Ankyrin Repeat Proteins (DARPins) can be selected to be high affinity binders to targets. The DARPin H10-2-G3 has been evolved to bind with picomolar affinity to HER2. In this work, we modeled the structure of the complex between the DARPin H10-2-G3 and HER2 using computational macromolecular docking. After analyzing the structural interface between the two proteins, we validated the structural model by showing that HER2 mutations at the putative interface significantly reduce binding to the DARPin but have no effect on binding to Herceptin, a HER2-specific monoclonal antibody. The X-ray crystal structure of this complex was solved very recently and showed that the backbone RMSD between the computational model and the X-ray structure was  1.1 Angstroms. This work illustrates the utility of computational structural biology methodologies in elucidating the details of protein-protein interactions.