Table I. Summary of recent computer-based designed interactions.
Goal | Strategy | System | PDB codes | Ref |
---|---|---|---|---|
Interface de novo design | ||||
Target binding | Known hydrophobic groove, hotspots | Hemaglutinin | 3R2X | [32] |
Target binding | Known hydrophobic groove | GoLoco peptide, Gαil | 2XNS | [33] |
Target binding | Known hydrophobic groove | PAK1 | [12] | |
Target binding, multi- specificity |
Dataset-driven scoring of coiled-coils | bZIP coiled-coil | [8] | |
Fibril inhibition | Strand pairing and hydrophobic sidechains | Tau and PAP fibrils | [7] | |
Two-sided design | Aromatic sidechain hydrogen bond | Ankyrin and PH1109 | 3Q9U, 3Q9N, 3QA9 | [48] |
Homodimer | Strand pairing and hydrophobic sidechains | Native monomer | 3ZY7 | [38] |
Homodimer | Metal binding and hydrophobic sidechains | Native monomer | 3V1A, 3V1B, 3V1C, 3V1D, 3V1E, 3V1F |
[39] |
Heterotetramer | Nonnatural zinc chromophore | Heterotetramer coiled-coil | [43] | |
Transmembrane targeting |
GxxGxxG motif in a beta helix | Beta-peptide | [46] | |
Transmembrane | Porphyrin binding | Four-helix bundle | [42] | |
Octahedron, 24-mer | Hydrophobic sidechains, hydroxyl hbonds | Native trimer | 3VCD, 4DDF | [17] |
Tetrahedron, 12-mer | Hydrophobic sidechains | Native trimer | 4EGG, 4DCL | [17] |
Nanotube coating | Helix Ala/Gly interaction with carbon ring | Coiled-coil hexamer | 3S0R | [16] |
Array, P6 crystal | Superhelix stacking, GxxG helix | Previous trimer lattice | 3V86, 4DAC | [45] |
| ||||
Scaffold design for new binding complexes | ||||
Target binding | Grafting | HIV epitopes 2F5 and 4E10 | 3RPT, 3RU8 and 3RI0, 3RHU, 3RFN |
[3] |
Target binding | Grafting | MMP-14 and TIMP-2 | not released | [52] |
Target binding | PAK1 biosensor | Autoinhib. helical domain | [13] | |
Nanohedron | Genetic fusion, rigid helix linker | Native dimer, trimer, helix | 3VDX, 4D9J | [35,55] |
Arrays, 1D and 2D | Genetic fusion, rotational symmetry | (TEM, AFM data) | [56] | |
| ||||
Interface redesign | ||||
Specificity | Second-site suppressor mutations | GoLoco peptide and Gai, UbcH7 and E6AP |
[57] [14] |
|
Specificity | Flexible backbone design to replace Phe | GTPase/GEF (1KI1) | 3QBV | [14] |
Multi-specificity | Structure-based modeling and library screening |
Bcl-x(L) | [58] | |
Affinity | Noncanonical amino acid at a native interface | Calpain, calpastatin | [59] | |
Affinity | Sequence design with backbone perturbation | PDZ peptide and CAL | [2] | |
Affinity | Hydrophobic interface design | Cytochrome cb562 | 3HNI, 3HNJ, 3HNL | [60] |
Affinity | Two hydrophobic mutations | PCNA and polymerase | [9] | |
Homologous target | Computationally-directed library | Ubc12 and E6AP | [61] | |
Hexamer | Augmentation of coiled-coil tetramer | GCN4-p1 starting tetramer | 3R4A, 3R4H, 3R3K, 3R46, 3R48 |
[37] |
Metal switching | Replace native interactions with metal coordination residues |
Ferritin cage | 4DYX, 4DYY, 4DYZ, 4DZ0 |
[62] |