Structural insights for engineering binding proteins based on non-antibody scaffolds

Engineered binding proteins derived from non-antibody scaffolds constitute an increasingly prominent class of reagents in both research and therapeutic applications. The growing number of crystal structures of these ‘alternative’ scaffold-based binding proteins in complex with their targets illustrate the mechanisms of molecular recognition that are common among these systems and those unique to each. This information is useful for critically assessing and improving/expanding engineering strategies. Furthermore, the structural features of these synthetic proteins produced under tightly controlled, directed evolution deepen our understanding of the underlying principles governing molecular recognition.

► A total of 28 3-D structures of non-antibody binding protein/target complexes are now published.
► The structures show scaffold-specific and universal trends in recognition mechanisms.
► The structures guide combinatorial library designs.