Figure 7.

Comparison of possible β-structures. Each β-strand is shown as an arrow and is composed of four polar (○) and three nonpolar (●) residues arranged in an alternating pattern (○●○●○●○). (Upper) If two successive β-strands were joined by an odd number of turn residues (three “t”s), then failure to form the desired hairpin could produce a continuous double-length amphiphilic β-strand with polar residues (○) pointing down toward the aqueous phase and nonpolar residues (●) pointing up toward the air. (Lower) Double-length amphiphilic β-strands are disfavored by “negative design.” Incorporating an even number of turn residues (four “t”s) between successive β-strands disrupts the up–down nonpolar/polar patterning. Therefore, if the four turn residues failed to form the desired turn (as depicted in Figs. 1 and 6) but instead continued as β-structure, then the resulting polar/nonpolar patterning would be “flipped”, and the double-length β-strand would not form a continuous amphiphile. Hence, for sequences in this designed binary code library (see Figs. 1 and 2), structures containing double-length β-strands would be disfavored at an air/water interface.