TABLE 1.

Benchmark datasets

Binding interaction	Benchmark name	Proteins in the set	Known functional sequences
Protein/small molecule	Cofactor	Seven protein families each binding a different cofactor	Natural sequence alignments, taken from Reference 42
	Enzyme specificity	10 enzymes	Experimentally-characterized point mutations that switch substrate specificity, taken from Reference 42
	DIG10	Computationally designed protein binding digoxigenin	Amino acid frequencies derived from deep sequencing of a site saturation mutagenesis library after three rounds of selection for binding to digoxigenin, from Reference 15
	Fen49	Computationally designed protein binding fentanyl	Amino acid frequencies derived from deep sequencing of a single site saturation mutagenesis library after four rounds of selection for binding to fentanyl, from Reference 48
Protein/protein	hGH/hGHR	Protein-protein complex of human growth hormone (hGH) binding to its receptor (hGHR)	Sequences of clones selected from five combinatorial libraries of hGH (average of 180 sequenced clones per library) after two rounds of selection for binding to hGHR, from Reference 50
	Herceptin/HER2	Protein-protein complex of Herceptin binding to HER2	Sequences of clones selected from four combinatorial libraries of Herceptin (average of 70 sequenced clones per library) after four rounds of selection for binding to HER2, from Reference 52