Fig. 1: Computational design of TLR3 minibinders.

a Left, TLR3 is natively dimerized and activated by dsRNA (PDB ID: 7WV5). Right, two hydrophobic patches on the TLR3 monomer were targeted for minibinder design (PDB ID: 1ZIW). b Polyvaline scaffolds were used in the RifDock pipeline to design de novo miniprotein binders. Several structural metrics were used as filters to select 23,789 designs for experimental screening. c Binders were identified using yeast surface display. During Sort 5, binding was clearly observed at 150 nM receptor but approached levels of background signal at 100 nM.