Fig. 2: Computationally and rationally designed αHBs as arrayed in the sensor.

The four groups of αHB used in the αHB sensor arrays are shaded by group: Group I, hydrophobic (yellow); Group II, polar-uncharged (green); Group III, polar-charged (blue); and Group IV, aromatic (red). Colored models and PDB entry codes are given for those αHB where X-ray crystal structures were obtained; otherwise, the models shown (gray) were built and optimized using CCBuilder2.0³⁵. In detail (see Supplementary Table 1), the sixteen Group I peptides included: previous designs for a pentamer, 3 hexamers, 2 heptamers and an octamer all verified by X-ray crystallography;^27,29 single and/or double mutations to Ala and Gly at central a and d sites to generate larger channels; a single-Pro mutant at the final d site to kink and open the C-terminal end of the channel; and a variant with all a sites made Met to vary the hydrophobic chemistry used. The eleven Group II peptides comprised: single mutants to Cys, His, Asn, Ser or Thr at d sites; and double mutations to His, Asn, Ser or Thr at consecutive a and d sites. The twelve Group III peptides had positively and negatively charged side chains, Lys and Glu, incorporated either singly or paired at a and d sites; and a single peptide with Asp at d. Finally, seven Group IV designs incorporated single Tyr at a or d sites, or Trp residues at a sites.