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]