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Engineering Protein Scaffolds for Molecular Recognition

Antibodies are effectively used in therapeutic, diagnostic, and biotechnology applications because of their high affinity and specificity in target binding. The goal of this research is to develop alternative proteins that mimic the molecular recognition ability of antibodies while providing distinct benefits. Specifically, protein scaffolds with high stability, low molecular weight, and efficient production capability are considered. Of particular interest is the tenth human fibronectin type III domain ( 10Fn3), a stable 10 kDa beta-sandwich protein. Yeast surface display will be used to select 10Fn3 variants that bind antigen with high affinity and specificity while maintaining advantageous biophysical properties. Engineering of the protein scaffolds will advance the understanding of molecular recognition and protein design in addition to providing a distinct alternative to antibodies for recognition, separation, and targeting applications.