Structural insights for engineering binding proteins based on non-antibody scaffolds
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Updated: May 20, 2026

Protein Engineering by Yeast Surface Display
Published on: November 29, 2024
Ryan N Gilbreth1, Shohei Koide
1Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA. skoide@uchicago.edu
Abstract:
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.
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