Figure 6. Covarying loop positions in EETI loop 3-substituted clones.

Coupled loop positions in enriched EL3-9 clones are shown linked with their respective z-scores. Covariance patterns and correlated pairs of amino acids at each of the coupled positions were used to predict sequences of EETI loop 3 variants that adopt the knottin fold. For purposes of generating predictions, position three was set to asparagine or threonine, and positions eight and nine were set to glycine and tyrosine, respectively.