Supplementary Table S1: PSI Set voting as sequence identity threshold of matched target pairs decreases.

Sequence Identity Cutoff

Correct Votes

Incorrect Votes

No Vote Winners

100

22

6

21

80

22

6

21

60

22

5

22

40

20

5

24

35

20

5

24

30

20

5

24

25

20

6

23

20

19

6

24

15

19

7

23

10

21

13

15

5

21

13

15

 

Supplementary Table S2: Training Set.

Protein

E.C. #

SCOP Class

SCOP Fold

Function

1rie_

1.10.2.2

b

ISP domain

RIESKE IRON-SULFUR PROTEIN

1mgtA

2.1.1.63

a,a/b

DNA/RNA-binding 3-helical bundle Ribonuclease H-like motif

O6-METHYLGUANINE-DNA METHYLTRANSFERASE

1eg2A

2.1.1.72

a/b

S-adenosyl-L-methionine-dependent methyltransferases

MODIFICATION METHYLASE RSRI

7mhtA

2.1.1.73

a/b

S-adenosyl-L-methionine-dependent methyltransferases

CYTOSINE-SPECIFIC METHYLTRANSFERASE HHAI

1jg1A

2.1.1.77

a/b

S-adenosyl-L-methionine-dependent methyltransferases

PROTEIN-L-ISOASPARTATE O-METHYLTRANSFERASE

1kpgA

2.1.1.79

a/b

S-adenosyl-L-methionine-dependent methyltransferases

CYCLOPROPANE-FATTY-ACYL-PHOSPHOLIPID SYNTHASE 1

1inlB

2.5.1.16

a/b

S-adenosyl-L-methionine-dependent methyltransferases

SPERMIDINE SYNTHASE

1g64B

2.5.1.17

a/b

P-loop containing nucleoside triphosphate hydrolases

COB(I)ALAMIN ADENOSYLTRANSFERASE

1e6bA

2.5.1.18

a,a/b

Glutathione S-transferase (GST), C-terminal domain Thioredo

GLUTATHIONE S-TRANSFERASE

1f2eA

2.5.1.18

a,a/b

Glutathione S-transferase (GST), C-terminal domain Thioredo

GLUTATHIONE S-TRANSFERASE

1gsfA

2.5.1.18

a,a/b

Glutathione S-transferase (GST), C-terminal domain Thioredo

GLUTATHIONE TRANSFERASE A1-1

6gsvA

2.5.1.18

a,a/b

Glutathione S-transferase (GST), C-terminal domain Thioredo

MU CLASS GLUTATHIONE S-TRANSFERASE OF ISOENZYME 3-3

1bdyA

2.7.1.37

b

PH domain-like

PROTEIN KINASE C

1iasA

2.7.1.37

small

Cystine-knot cytokines

TGF-BETA RECEPTOR TYPE I

1qf8A

2.7.1.37

b

Galactose-binding domain-like

CASEIN KINASE II

1rgs_

2.7.1.37

b

C2 domain-like

CAMP DEPENDENT PROTEIN KINASE

1b55B

2.7.1.112

a+b

Protein kinase-like (PK-like)

TYROSINE-PROTEIN KINASE BTK

1fltW

2.7.1.112

small

Rubredoxin-like

VASCULAR ENDOTHELIAL GROWTH FACTOR

1nukA

2.7.1.112

 

 

TYROSINE-PROTEIN KINASE RECEPTOR EPH

1nksA

2.7.4.3

a/b

P-loop containing nucleoside triphosphate hydrolases

ADENYLATE KINASE

1nskL

2.7.4.6

a+b

Ferredoxin-like

NUCLEOSIDE DIPHOSPHATE KINASE

1jxiA

2.7.4.7

a/b

Ribokinase-like

PHOSPHOMETHYLPYRIMIDINE KINASE

1c25_

3.1.3.48

a/b

Rhodanese/Cell cycle control phosphatase

CDC25A

1gwz_

3.1.3.48

a/b

(Phosphotyrosine protein) phosphatases II

SHP-1

1j4xA

3.1.3.48

a/b

(Phosphotyrosine protein) phosphatases II

DUAL SPECIFICITY PROTEIN PHOSPHATASE 3

1cen_

3.2.1.4

b,a/b

WW domain-like TIM beta/alpha-barrel FKBP-like

CELLULASE CELC

1edg_

3.2.1.4

b

Single-stranded right-handed beta-helix

ENDOGLUCANASE A

2nlrA

3.2.1.4

a+b

Lysozyme-like

ENDOGLUCANASE

7a3hA

3.2.1.4

a+b

Lysozyme-like

ENDOGLUCANASE

1i8a_

3.2.1.8

b

6-bladed beta-propeller

ENDO-1,4-BETA-XYLANASE A

1ukrA

3.2.1.8

a/b

TIM beta/alpha-barrel

ENDO-1,4-B-XYLANASE I

1goiA

3.2.1.14

a/b

TIM beta/alpha-barrel

CHITINASE B

1czfA

3.2.1.15

b

Concanavalin A-like lectins/glucanases

POLYGALACTURONASE II

1d9uA

3.2.1.17

a/b

TIM beta/alpha-barrel

BACTERIOPHAGE LAMBDA LYSOZYME

3lzt_

3.2.1.17

 

 

LYSOZYME

1f8eA

3.2.1.18

b

Concanavalin A-like lectins/glucanases

NEURAMINIDASE

1fr6A

3.5.2.6

mult

beta-lactamase/transpeptidase-like

BETA-LACTAMASE

1k55A

3.5.2.6

mult

beta-lactamase/transpeptidase-like

BETA LACTAMASE OXA-10

1pioA

3.5.2.6

mult

beta-lactamase/transpeptidase-like

BETA-LACTAMASE

1juk_

4.1.1.48

a/b

TIM beta/alpha-barrel

INDOLE-3-GLYCEROL PHOSPHATE SYNTHASE

1ayl_

4.1.1.49

 

 

PHOSPHOENOLPYRUVATE CARBOXYKINASE

1jl0B

4.1.1.50

a+b

S-adenosylmethionine decarboxylase

S-ADENOSYLMETHIONINE DECARBOXYLASE PROENZYME

2ahjA

4.2.1.84

a+b

Nitrile hydratase alpha chain

NITRILE HYDRATASE

1dcpA

4.2.1.96

a+b

DCoH-like

DCOH

1ep0A

5.1.3.13

b

Double-stranded beta-helix

DTDP-6-DEOXY-D-XYLO-4-HEXULOSE 3,5-EPIMERASE

1eq2H

5.1.3.20

a/b

NAD(P)-binding Rossmann-fold domains

ADP-L-GLYCERO-D-MANNOHEPTOSE 6-EPIMERASE

1a41_

5.99.1.2

a+b

DNA breaking-rejoining enzymes

TOPOISOMERASE I

1cy4A

5.99.1.2

mult

Prokaryotic type I DNA topoisomerase

DNA TOPOISOMERASE I

1ej9A

5.99.1.2

a+b,mult

DNA breaking-rejoining enzymes Eukaryotic DNA topoisomerase

DNA TOPOISOMERASE I

1vcc_

5.99.1.2

a+b

DNA topoisomerase I domain

DNA TOPOISOMERASE I

1fpmA

6.3.4.3

a/b

P-loop containing nucleoside triphosphate hydrolases

FORMATE--TETRAHYDROFOLATE LIGASE

1dj3A

6.3.4.4

a/b

P-loop containing nucleoside triphosphate hydrolases

ADENYLOSUCCINATE SYNTHETASE

1k92A

6.3.4.5

a/b,a+b

Adenine nucleotide alpha hydrolase-like Argininosuccinate s

ARGININOSUCCINATE SYNTHASE

                                               

Supplementary Table S3: PDB Set.

Protein

E.C. #

SCOP Class

SCOP Fold

Function

1hdoA

1.3.1.24

a/b

NAD(P)-binding Rossmann-fold domains

BILIVERDIN IX BETA REDUCTASE

1b26A

1.4.1.3

a/b

NAD(P)-binding Rossmann-fold domains

GLUTAMATE DEHYDROGENASE

1kmvA

1.5.1.3

a/b

Dihydrofolate reductases

DIHYDROFOLATE REDUCTASES, EUKARYOTIC TYPE

1l1dA

1.8.4.5

b

Mss4-like

C-TERMINAL MSRB DOMAIN OF PEPTIDE METHIONINE SULFOXIDE REDUCTASE PILB

1v54J

1.9.3.1

mem

Single transmembrane helix

MITOCHONDRIAL CYTOCHROME C OXIDASE SUBUNIT VIIA

1eb7A

1.11.1.5

a

Cytochrome c

DI-HEME CYTOCHROME C PEROXIDASE

1lycA

1.11.1.7

a

Heme-dependent peroxidases

FUNGAL PEROXIDASE (LIGNINASE)

1hqi_

1.14.13.7

a+b

Monooxygenase (hydroxylase) regulatory protein

PHENOL HYDROXYLASE P2 PROTEIN

1oykA

1.14.99.3

a

Heme oxygenase-like

HEME OXYGENASE-1 (HO-1)

1m1nA

1.18.6.1

a/b

Chelatase-like

NITROGENASE IRON-MOLYBDENUM PROTEIN, ALPHA CHAIN

1orhA

2.1.1.125

a/b

S-adenosyl-L-methionine-dependent methyltransferases

PROTEIN ARGININE N-METHYLTRANSFERASE 1, PRMT1

1ib1A

2.3.1.87

a

alpha-alpha superhelix

14-3-3 PROTEIN, ZETA ISOFORM

1o7qA

2.4.1.151

a/b

Nucleotide-diphospho-sugar transferases

ALPHA-1,3-GALACTOSYLTRANSFERASE CATALYTIC DOMAIN

1nh7A

2.4.2.17

a/b

Periplasmic binding protein-like II

ATP PHOSPHORIBOSYLTRANSFERASE (ATP-PRTASE, HISG), CATALYTIC DOMAIN

1fsgA

2.4.2.8

a/b

PRTase-like

HYPOXANTHINE-GUANINE-XANTHINE PRTASE

6pfkA

2.7.1.11

a/b

Phosphofructokinase

ATP-DEPENDENT PHOSPHOFRUCTOKINASE

1r79A

2.7.1.107

small

Cysteine-rich domain

DIACYLGLYCEROL KINASE DELTA

1bx4A

2.7.1.20

a/b

Ribokinase-like

ADENOSINE KINASE

1rdqE

2.7.1.37

a+b

Protein kinase-like (PK-like)

CAMP-DEPENDENT PK, CATALYTIC SUBUNIT

1pdo_

2.7.1.69

a/b

IIA domain of mannose transporter, IIA-Man

IA DOMAIN OF MANNOSE TRANSPORTER, IIA-MAN

1m15A

2.7.3.3

a

Guanido kinase N-terminal domain

ARGININE KINASE, N-DOMAIN

1jxiA

2.7.4.7

a/b

Ribokinase-like

HMP-PHOSPHATE KINASE, THID

1ef4A

2.7.7.6

a

DNA/RNA-binding 3-helical bundle

RNA POLYMERASE SUBUNIT RPB10

1p16A

2.7.7.50

a+b

ATP-grasp

MRNA CAPPING ENZYME ALPHA SUBUNIT

1f7lA

2.7.8.7

a+b

4'-phosphopantetheinyl transferase

HOLO-(ACYL CARRIER PROTEIN) SYNTHASE ACPS

1okgA

2.8.1.2

a+b

FKBP-like

3-MERCAPTOPYRUVATE SULFURTRANSFERASE

1ksjB

3.1.4.17

b

Immunoglobulin-like beta-sandwich

GMP-PDE DELTA

1jl1A

3.1.26.4

a/b

Ribonuclease H-like motif

RNASE H (RNASE HI)

1i0vA

3.1.27.3

a+b

Microbial ribonucleases

RNASE T1

1hx0A

3.2.1.1

a/b

TIM beta/alpha-barrel

ANIMAL ALPHA-AMYLASE

1ks8A

3.2.1.4

a

alpha/alpha toroid

ENDO-B-1,4-GLUCANASE

3sil_

3.2.1.18

b

6-bladed beta-propeller

SALMONELLA SIALIDASE

1es5A

3.4.16.4

mult

beta-lactamase/transpeptidase-like

D-ALA CARBOXYPEPTIDASE/TRANSPEPTIDASE

1bcrA

3.4.16.6

a/b

alpha/beta-Hydrolases

SERINE CARBOXYPEPTIDASE II

1pq7A

3.4.21.4

b

Trypsin-like serine proteases

TRYPSIN(OGEN)

2hrvA

3.4.22.29

b

Trypsin-like serine proteases

2A CYSTEINE PROTEINASE

1gk9A

3.5.1.11

a+b

Ntn hydrolase-like

PENICILLIN ACYLASE

1uf4A

3.5.1.77

a+b

Carbon-nitrogen hydrolase

N-CARBAMOYL-D-AMINOACID AMIDOHYDROLASE

1sg3A

3.5.3.4

b

Galactose-binding domain-like

ALLANTOICASE

1i40A

3.6.1.1

b

OB-fold

INORGANIC PYROPHOSPHATASE

1opzA

3.6.3.4

a+b

Ferredoxin-like

POTENTIAL COPPER-TRANSLOCATING P-TYPE ATPASE COPA (YVGX)

1hxgA

4.1.99.7

a

alpha/alpha toroid

5-EPI-ARISTOLOCHENE SYNTHASE

1iv3A

4.6.1.12

a+b

Bacillus chorismate mutase-like

2C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE SYNTHASE ISPF

1pinA

5.2.1.8

a+b

FKBP-like

MITOTIC ROTAMASE PIN1, DOMAIN 2

1dl3A

5.3.1.24

a/b

TIM beta/alpha-barrel

N-(5'PHOSPHORIBOSYL)ANTRANILATE ISOMERASE, PRAI

1fztA

5.4.2.1

a/b

Phosphoglycerate mutase-like

PHOSPHOGLYCERATE MUTASE

1n3lA

6.1.1.1

a/b

Adenine nucleotide alpha hydrolase-like

TYROSYL-TRNA SYNTHETASE (TYRRS)

1pfvA

6.1.1.10

a/b

Adenine nucleotide alpha hydrolase-like

METHIONYL-TRNA SYNTHETASE (METRS)

1sbqA

6.3.3.2

a/b

NagB/RpiA/CoA transferase-like

5,10-METHENYLTETRAHYDROFOLATE SYNTHETASE HOMOLOG MPN348

                                               

Supplementary Table S4: PSI Set.

Protein

E.C. #

SCOP Class

SCOP Fold

Function

1z82A

1.1.1.8

-

not available

GLYCEROL-3-PHOSPHATE DEHYDROGENASE

1nvtA

1.1.1.25

a/b

Aminoacid dehydrogenase-like, N-terminal domain

SHIKIMATE 5-DEHYDROGENASE AROE

1zejA

1.1.1.35

-

not available

3-HYDROXYACYL-COA DEHYDROGENASE

1spxA

1.1.1.47

a/b

NAD(P)-binding Rossmann-fold domains

GLUCOSE DEHYDROGENASE

1yb4A

1.1.1.60

-

not available

TARTRONIC SEMIALDEHYDE REDUCTASE

2amfA

1.2.1.5

-

not available

1-PYRROLINE-5-CARBOXYLATE REDUCTASE

1txnA

1.3.3.3

-

not available

COPROPORPHYRINOGEN III OXIDASE

1vllA

1.4.1.1

a/b

NAD(P)-binding Rossmann-fold domains

ARCHAEAL ALANINE DEHYDROGENASE

1ooeA

1.6.99.7

a/b

NAD(P)-binding Rossmann-fold domains

DIHYDROPTERIDIN REDUCTASE (PTERIDINE REDUCTASE)

1nni1

1.7.1.6

a/b

Flavodoxin-like

AZOBENZENE REDUCTASE

1p91A

2.1.1.51

a/b

S-adenosyl-L-methionine-dependent methyltransferases

RRNA METHYLTRANSFERASE RLMA

2ar0A

2.1.1.72

-

not available

TYPE I RESTRICTION ENZYME ECOKI M PROTEIN

1vloA

2.1.2.10

a+b

Aminomethyltransferase folate-binding domain

GLYCINE CLEAVAGE SYSTEM T PROTEIN, GCVT

1vlvA

2.1.3.3

a/b

ATC-like

ORNITHINE TRANSCARBAMOYLASE

1vmiA

2.3.1.8

-

not available

PUTATIVE PHOSPHATE ACETYLTRANSFERASE

1vlpA

2.4.2.11

a+b

alpha/beta-Hammerhead

NICOTINATE PHOSPHORIBOSYLTRANSFERASE, C-TERMINAL DOMAIN

1yirA

2.4.2.11

-

not available

NICOTINATE PHOSPHORIBOSYLTRANSFERASE 2

1xi3A

2.5.1.3

a/b

TIM beta/alpha-barrel

THIAMIN PHOSPHATE SYNTHASE

1iy9A

2.5.1.16

a/b

S-adenosyl-L-methionine-dependent methyltransferases

SPERMIDINE SYNTHASE

1vjoA

2.6.1.44

a/b

PLP-dependent transferases

ALANINE-GLYOXYLATE AMINOTRANSFERASE

1xx6A

2.7.1.21

-

not available

THYMIDINE KINASE

1kagA

2.7.1.71

a/b

P-loop containing nucleoside triphosphate hydrolases

SHIKIMATE KINASE (AROK)

2akoA

2.7.2.11

-

not available

GLUTAMATE 5-KINASE

1ej2A

2.7.7.1

a/b

Adenine nucleotide alpha hydrolase-like

NICOTINAMIDE MONONUCLEOTIDE (NMN) ADENYLYLTRANSFERASE

1r1dA

3.1.1.1

a/b

alpha/beta-Hydrolases

CARBOXYLESTERASE

1vl1A

3.1.1.31

a/b

NagB/RpiA/CoA transferase-like

6-PHOSPHOGLUCONOLACTONASE

1vjvA

3.1.2.15

a+b

Cysteine proteinases

UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 6

1xm8A

3.1.2.6

-

not available

GLYOXALASE II

1vr0A

3.1.3.71

-

not available

PROBABLE 2-PHOSPHOSULFOLACTATE PHOSPHATASE

1nxcA

3.2.1.113

a

alpha/alpha toroid

CLASS I ALPHA-1;2-MANNOSIDASE, CATALYTIC DOMAIN

1o0xA

3.4.11.18

a+b

Creatinase/aminopeptidase

METHIONINE AMINOPEPTIDASE

1o59A

3.5.3.4

b

Galactose-binding domain-like

ALLANTOICASE

1xfkA

3.5.3.8

-

not available

FORMIMIDOYLGLUTAMASE

1xsrA

3.5.3.19

-

not available

UREIDOGLYCOLATE HYDROLASE

1yvwA

3.6.1.31

-

not available

PHOSPHORIBOSYL-ATP PYROPHOSPHATASE

1tufA

4.1.1.20

a/b

TIM beta/alpha-barrel

DIAMINOPIMELATE DECARBOXYLASE LYSA

1fi4A

4.1.1.33

a+b

Ribosomal protein S5 domain 2-like

MEVALONATE 5-DIPHOSPHATE DECARBOXYLASE

1vpjA

4.2.1.2

-

not available

FUMARASE

1kmjA

4.4.1.16

a/b

PLP-dependent transferases

NIFS-LIKE PROTEIN/SELENOCYSTEINE LYASE

1kmkA

4.4.1.16

a/b

PLP-dependent transferases

NIFS-LIKE PROTEIN/SELENOCYSTEINE LYASE

1y0eA

5.1.3.9

-

not available

PUTATIVE N-ACETYLMANNOSAMINE-6-PHOSPHATE 2-EPIMERASE

1o8bA

5.3.1.6

a/b

NagB/RpiA/CoA transferase-like

D-RIBOSE-5-PHOSPHATE ISOMERASE (RPIA), CATALYTIC DOMAIN

1x8mA

5.3.1.17

b

Double-stranded beta-helix

5-KETO-4-DEOXYURONATE ISOMERASE KDUI

1ou0A

5.4.1.2

a/b

Flavodoxin-like

PRECORRIN-8X METHYLMUTASE RELATED PROTEIN

1m0tA

6.3.2.3

a+b

ATP-grasp

EUKARYOTIC GLUTATHIONE SYNTHETASE

1kutA

6.3.2.6

a+b

SAICAR synthase-like

SAICAR SYNTHASE

1pzvA

6.3.2.19

a+b

UBC-like

UBIQUITIN CONJUGATING ENZYME, UBC

1vl2A

6.3.4.5

a+b

Argininosuccinate synthetase, C-terminal domain

ARGININOSUCCINATE SYNTHETASE

1vkzA

6.3.4.13

a+b

ATP-grasp

GLYCINAMIDE RIBONUCLEOTIDE SYNTHETASE (GAR-SYN)