TABLE I.

Overview of CASP5 Targets

Target ID	Lengtha	Name species	PDBb method	Domains rangec	CASP classd	Descriptione
T0129	182	HI0817 H. influenzae	— X-ray	single	NF	Novel fold composed of seven helices. First four helices form a distorted up-and- down bundle, whereas the rest assemble as a 3-helical left-handed bundle. Helix 2 and helix 5 form a tight interaction.
T0130	114	HI0073 H. influenzae	— X-ray		CM/FR(H)	Nucleotidyltransferase superfamily. Sequence finds PDB (18% 1fa0, Dali z score 5.0) with transitive PSI-BLAST. Compared to 1fa0, the structure contains generally shorter structural elements, loses an edge β-hairpin, and retains the active site.
T0131	100	HI0857 H. influenzae	— X-ray	single	not used	Preliminary version of the structure. No side-chain assignments. Not used for assessment.
T0132	154	HI0827 H. influenzae	— X-ray	single	CM/FR(H)	Thioesterase superfamily member. Sequence finds 4-Hydroxybenzoyl CoA Thioesterase (16%, 1bvq, Dali z score 13.4) with transitive PSI-BLAST.
T0133	312	HIP1R N-terminal domain rat	— X-ray	single	CM/FR(H)	α/α superhelix fold, same family as N- terminal domain of phosphoinositide- binding clathrin adaptor (13% 1hg5).
T0134	251	δ-adaptin appendage domain human	— X-ray	T0134_1:A878- A1006 T0134_2:A1007- A1112	FR(H) FR(H)	Shares domain structure with remote homologue clathrin adaptor appendage domain (12% 1qts). Homology inferred from structural similarity (Dali z score 19.1). N-terminal domain related to g1-adaption ear domain (1 gyu).
T0135	108	Boiling stable protein P. tremula	— X-ray	single	FR(A)	Ferredoxin-like fold analog. Contains broken helix with conserved residues not found in current ferredoxin-like fold superfamilies. A tight dimer with two β-sheets forming a barrel, dimer structure is similar to C-terminal domains of Lrp/AsnC-like transcriptional regulator (1i1g) and Muconalactone isomerase (1mli). eEF- 1beta-like domain (6% 1b64) aligns with Dali z score 3.2.
T0136	523	Transcarboxylase 12S subunit P. shermanii	1on3 1on9 X-ray	T0136_1: E4-E259 T0136_2: E260-E523	CM/FR(H) CM/FR(H)	Duplication of a Clp/crotonase-like domain. Two domains are closer to each other than to any known structure and share an additional ααββ-unit at the N-terminus. Each domain finds PDB (12–13%, 1dub) with transitive PSI- BLAST. Closest PDB structure 1nzy, Dali z score 14.1 and 13.2 for domains 1 and 2.
T0137	133	Fatty acid binding protein E. granulosus	1o8v X-ray	single	CM	Fatty acid-binding protein family (43% 2ans).
T0138	135	KaiA N-terminal domain S. elongatus	1m2e 1m2f NMR	single	FR(H)	Flavodoxin-like fold, CheY-like superfamily (19% 1kgs). Homology interference based on structural similarity (Dali z score 13.2).
T0139	83	Fragmentation factor/Caspase inhibitor DNase domain human	1koy NMR	single	not used	Novel fold with irregular array of four helices. Some topological similarity to existing structures (e.g., 1a9x_A:419- 481). Information about the structure available before the target expired. Not used in assessment.
T0140	103	1B11 synthetic protein	— X-ray	single, composite of 2 chains B18-B74, A74- A102	CM	Synthetic protein composed of cold shock protein A (N-terminal) and E. coli 30S ribosomal subunit protein S1 (C- terminal). Although each parent structure forms an OB-fold, the synthetic protein forms an OB-fold-like swapped-dimer.
T0141	187	AmpD C. freundii	1iya NMR	single	CM/FR(H)	Homologue of T7 lysozyme (26% 1lba). Unexpected structural differences in active site.
T0142	282	Nitrophorin C. lectularius	— X-ray	single	CM	DNaseI-like fold, Inositol polyphosphate 5-phosphatase family (26% 1i9z).
T0143	216	V8 protease S. aureus	— X-ray	T0143_1:1-20, 116-216 T0143_2:21-115	CM CM	Trypsin-like serine protease composed of two domains treated as a single unit (28% 1agj).
T0144	172	CYP protein L. luteus	— X-ray	—	not used	N/A
T0145	216	Gliotactin C-terminus D. melanogaster	— X-ray	—	not used	No coordinates; “natively unfolded” protein.
T0146	325	ygfZ E. coli	— X-ray	T0146_1:A1- A24, A114-A196 T0146_2: A25-A113 T0146_3: A244-A299	FR(A)/NF FR(A)/NF FR(A)/NF	Three domains: Domains 1 and 2 in tight contact and represent a potential duplication of a ferredoxin-like unit with an additional β-strand inserted at the edge of the β-sheet. Domain 1 is circularly permuted with respect to domain 2. No side-chain assignments for domain 3. Domains 2 and 3 connected by a sequence-conserved linker.
T0147	245	ycdX E. coli	1m65 1m68 X-ray	single	FR(A)	PHP domain, a seven-stranded version of a TIM β/α-barrel fold. Possible remote homologue of metallohydrolases (12% 1k6w, Dali z score 8.1), with which it shares a metal-binding site.
T0148	163	HI1034 H. influenzae	1in0 X-ray	T0148_1:A2-A9, A101-A163 T0148_2: A10-A100	FR(A) FR(A)	Tandem repeat of a ferredoxin-like fold with swapped N-terminal strands. Each domain is a possible remote homologue of Ribosome recycling factor α+β domain (11%, 15% 1ek8).
T0149	318	yjiA E. coli	1nij X-ray	T0149_1: A2-A202 T0149_2: A203-A318	CM/FR(H) NF	Two domains: N-terminal Nitrogenase iron protein family (17% 1j8m). C- terminal novel fold with some structural similarity to 1ah6, 1ebf_B: 149-337, 1ptf and target T0187_1.
T0150	102	Ribosomal protein L30E T. celer	1h7m X-ray	single	CM	L30e/L7ae ribosomal protein family (34% 1ck2).
T0151	164	Single-strand binding protein M. tuberculosis	— X-ray	single	CM	ssDNA-binding protein, OB-fold (30% 1qvc).
T0152	210	Hypothetical protein Rv1347c M. tuberculosis	— X-ray	single	CM/FR(H)	Acyl-CoA N-actyltransferase (NAT) family (15% 1ild). Typical for this family b-bulge in the active site lacks in this protein leading to a different shape of the β-sheet.
T0153	154	dUTPase M. tuberculosis	1mq7 X-ray	single	CM	dUTPase, beta-clip fold (35% leu5).
T0154	309	Pantothenate synthetase M. tuberculosis	1mop- X-ray	T0154_1: A3-A187 T0154_2: A188-A290	CM CM	PanC, Adenine nucleotide α-hydrolase- like fold (35%, 49% iho), proteins share domain structure.
T0155	133	Probable dihydroneopterin aldolase M. tuberculosis	— X-ray	single	CM	7,8-dihidroneopterin aldolase, T-fold (33% 1dhn).
T0156	157	Probable SAM-dependent methyltransferase M. tuberculosis	— X-ray	single	FR(H)	Phosphohistidine domain superfamily, the “swiveling” domain fold (14% 1 dik, Dali z score 7.5). Homology inferred from structural similarity.
T0157	138	yqgF E. coli	— X-ray	single	FR(H)	Ribonuclease H-like superfamily (15% 1hjr Dali z score 9.6). Homology inferred from the presence of described RNaseH motifs.
T0158	319	Actyl esterase E. coli	— X-ray	—	not used	N/A
T0159	309	Glycine betaine-binding protein E. coli	— X-ray	T0159_1:X1- X91, X234-X309 T0159_2: X92-X233	CM/FR(H) CM/FR(H)	Periplasmic-binding protein I-like superfamily. Two domains with different relative orientation than closest homologue (8% 1gr2). Transitive PSI-BLAST searches establish homology.
T0160	128	VAP-A protein rat	— X-ray	single	CM	Major sperm protein family, Immunoglobulin-like fold (22% 2msp).
T0161	156	HI1480 H. influenzae	— X-ray	single	NF	New fold, α-helical array capped with a curved three-stranded β-sheet.
T0162	286	F-actin capping protein a-1 subunit chicken	1izn X-ray	T0162_1: A7-A62 T0162_2: A63-A113 T0162_3: A114-A281	FR(A) FR(A) NF	Three domains: N-terminal three-helical bundle, middle possible rubredoxin-like zinc finger that lost zinc ligands (9% 1rfs), C-terminal novel fold five- stranded meander flanked by two helices.
T0163	369	Glycin oxidase B. subtilis	— X-ray	—	not used	N/A
T0164	166	C20	— X-ray	—	not used	cancelled
T0165	318	Cephalosporin C deacetylase B. subtilis	117a X-ray	single	CM/FR(H)	α/β-hydrolase superfamily (18% 1a8s).
T0166	150	SLYA E. faecalis	— X-ray	—	not used	cancelled
T0167	185	Hypothetical cytosolic protein yckF B. subtilis	1m3s X-ray	single	CM	SIS domain (39% 1jeo).
T0168	327	Glutaminase B. subtilis	1mki X-ray	T0168_1:A1- A68, A210-A327 T0168_2: A69-A209	CM/FR(H) CM/FR(H)	Domain structure shared by β- Lactamase/D-ala carboxypeptidase superfamily (7% 1fof). Found by transitive PSI-BLAST.
T0169	156	yqjY B. subtilis	1mk4 X-ray	single	CM/FR(H)	N-acetyl transferase (NAT) family (9% 1bo4).
T0170	69	FF domain of HYPA/FBP11 human	1h40 NMR	single	FR(A)/NF	Three-helical bundle capped by a 3_10 helix, new fold, structural similarity to Phosphatase 2C C-terminal domain (1a6q:297-368) and three-helical DNA/ RNA-biding bundles.
T0171	256	Protein BioH E. coli	1m33 X-ray	—	not used	N/A
T0172	299	Conserved hypothetical protein MRAW T. maritima	1m6y 1n2x X-ray	T0172_1:A2- A115, A217-A294 T0172_2: A116-A216	CM/FR(H) FR(A)/NF	SAM-dependent methyltransferase (16% 1jg2) with an inserted SAM-like fold domain (15% 1cuk).
T0173	303	Mycothiol deacetylase M. tuberculosis	— X-ray	single	FR(A)/NF	Novel Rossmann-like α/β fold with topological similarity to SAM methyltransferases but distinct curvature of the β-sheet.
T0174	417	Protein XO1-1 C. elegans	1mg7 X-ray	T0174_1:B8- B28, B199-B374 T0174_2: B39-B198	FR(H) FR(H)	GHMP kinase family, homology inferred from structural similarity (9% 1kvk, Dali z score 18.5).
T0175	248	Hypothetical protein yjhP E. coli	1nkv X-ray	—	not used	N/A
T0176	100	Hypothetical protein yggU E. coli	1n91 X-ray	single	CM	Close homologue of hypothetical protein MTH637 (26% 1jrm).
T0177	240	Hypothetical protein HP0162 H. pylori	1mw7 X-ray	T0177_1: A21-A77 T0177_2: A78-A130, A206-A240 T0177_3: A131-A205	CM CM CM	YebC-like family (30% 1kon), proteins share the domain structure.
T0178	219	Deoxyribose-phosphate aldolase A. aeolicus	1mzh X-ray	single	CM	Deoxyribose-phosphate aldolase DeoC, TIM-barrel (27% 1jcl).
T0179	276	Spermidine synthase homolog B. subtilis	liy9 X-ray	T0179_1:A2-A57 T0179_2: A58-A275	CM CM	Spermidine synthase (43% 1 inl), proteins share domain structure, SAM- dependent methyltransferase homologue.
T0180	53	Hypothetical protein MTH467 M. thermoautotrophicum	— NMR	—	not used	N/A
T0181	111	Hypothetical protein YHR087w S. cerevisiae	1nyn X-ray	single	NF	New fold, curved antiparallel β-sheet with 4 α-helices on one side, unusual topology.
T0182	250	TM1478 T. maritima	1o0x X-ray	single	CM	Methionine aminopeptidase (42% 2mat).
T0183	248	TM1559 T. maritima	1o0y X-ray	single	CM	Deoxyribose-phosphate aldolase DeoC, TIM-barrel (30% 1jcl).
T0184	240	TM1102 T. maritima	1o0w X-ray	T0184_1: B1-B165 T0184_2: B166-B236	CM CM/FR(H)	Two domains: N-terminal RNase III endonuclease domain (35% 1jfz). C- terminal dsRNA-binding domain (26% 1di2).
T0185	457	TM0231 T. maritima	1j6u X-ray	T0185_1: A1-A101 T0185_2: A102-A298 T0185_3: A299-A446	CM/FR(H) CM CM/FR(H)	MurD-like family (22% 3uag), proteins share domain structure. P-loop in the middle domain.
T0186	364	TM0814 T. maritima	1o12 X-ray	T0186_1:A1- A44, A331-A363 T0186_2: A45-A256, A293-A330 T0186_3: A257-A292	CM CM/FR(H) FR(A)/NF	Metallohydrolase superfamily, TIM β/α- barrel catalytic domain (domain 2, 25% 1gkp), shares “composite” domain with some homologues (domain 1, 13% 1gkp). Interesting dwarf insertion domain, unique to this protein, potential deteriorated rubredoxin-like zinc finger (domain 3, 13% 1kqs).
T0187	417	TM1585 T. maritima	1o0u X-ray	T0187_1:A4- 2A2, A250-A417 T0187_2: A23-A249	FR(A)/NF FR(A)	Two domains: N-terminal structurally similar to Cobalt precorrin-4 methyltransferase C-terminal domain (8% 1cbf), C-terminal Rossmann-type fold (11% 1gpj). T0187_1 shares some topological similarity with T0149_2.
T0188	124	TM1816 T. maritima	1o13 X-ray	single	CM	Close homologue of hypothetical protein MTH1175, RNaseH-like fold (31% 1eo1).
T0189	319	TM0828 T. maritima	1o14 X-ray	single	CM/FR(H)	Ribokinase-like family (14% 1rk2).
T0190	114	Transthyretin-related protein E. coli	— X-ray	single	CM	Prokaryotic homologue of transthyretin (31% 1dvx).
T0191	282	Shikimate 5-dehydrogenase M. jannaschii	1nvt X-ray	T0191_1:A1- A104, A248-A282 T0191_2: A105-A247	FR(A) CM	Two different domains, N-terminal anticodon-binding domain-like fold (7% 1ati), C-terminal NAD(P)-binding Rossmann superfamily (22% 1gpj).
T0192	171	Spermidime/Spermine acetyltransferase human	— X-ray	single, composite of 2 chains: 2-153 (first chain), 154-171 (second chain)	CM/FR(H)	N-acetyl transferase (NAT) family, (16% 1qsm), domain-swapped last strands.
T0193	211	AT-rich DNA binding protein T. aquaticus	— X-ray	T0193_1:A1-A78 composite of 2 chains T0193_2: A79-A187 (first chain), B188-B209 (second chain)	FR(H) CM	Two different domains, N-terminal 3- helical bundle, winged HTH motif (29% 1j5y), PSI-BLAST detects structural similarity with E-values below threshold. C-terminal NAD(P)-binding Rossmann superfamily (17% 1ofg), domain-swapped last helix; closest template was given away as “Additional Information.”
T0194	237	Hypothetical protein Y450 M. pneumoniae	— X-ray	—	not used	The structure was solved not for the target sequence but for its homologue (~20%). Not used in assessment.
T0195	299	Hypothetical esterase in SMC3-MRPL8 intergenic region S. cerevisiae	— X-ray	single	CM/FR(H)	α/β-Hydrolase superfamily (18% 1jjf).

^aLength of the sequence provided for prediction.

^bPDB identifier for the structure is given, where known. In some cases, the structure is not yet published and has not been deposited with PDB.

^cDomain definitions refer to residue numbers in the 3D coordinate structure provided by the experimentalists.

^dSee text for discussion of class.

^eBrief discussion of the structure within the context of existing protein fold classifications, with possible evolutionary connections (see text for discussion). Where simple sequence similarity searches of the target against representative sequences of structures in the PDB yielded an unambiguous match, the percentage similarity and sample PDB identifiers are given.