FIGURE 3. Computational design models of the two most active catalysts.

a, KE59 uses indole-3-glycerolphosphate synthase from Sulfolobus solfataricus as a scaffold. The transition state model is almost completely buried, with loops covering the active site. The mostly hydrophobic residues in the active site pocket pack the transition state model tightly, providing high shape complementarity (shape complementarity = 0.84; ref. 29). The polar residue Ser 211 interacts with the nitro group of the transition state to promote binding. The key catalytic residues (Glu 231 and Trp 110) are depicted in cyan. b, The deoxyribose-phosphate aldolase from E. coli is the scaffold for KE70. The shorter loops leave the active-site pocket freely accessible for the substrate. The transition state is surrounded by hydrophobic residues that provide high shape complementarity (shape complementarity = 0.77; ref. 29). His 16 and Asp 44 (in cyan) constitute the catalytic dyad whereas Tyr 47 (in cyan) provides -stacking interactions.