TALOS: Protein backbone angle restraints from searching a database for chemical shift and sequence homology

Gabriel Cornilescu, Frank Delaglio and Ad Bax

Laboratory of Chemical Physics
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Bethesda, Maryland 20892-0520

Abstract: Chemical shifts of backbone atoms in proteins are exquisitely sensitive to local conformation, and homologous proteins show quite similar patterns of secondary chemical shifts. The inverse of this relation is used to search a database for triplets of adjacent residues with secondary chemical shifts and sequence similarity which provide the best match to the query triplet of interest. The database contains ¹³C^a, ¹³C^b, ¹³C',¹H^a and ¹⁵N chemical shifts for 20 proteins for which a high resolution X-ray structure is available. The computer program TALOS was developed to search this database for strings of residues with chemical shift and residue type homology. The relative importance of the weighting factors attached to the secondary chemical shifts of the five types of resonances relative to that of sequence similarity was optimized empirically. TALOS yields the 10 triplets which have the closest similarity in secondary chemical shift and amino acid sequence to those of the query sequence. If the central residues in these 10 triplets exhibit similar phi and psi backbone angles, their averages can reliably be used as angular restraints for the protein whose structure is being studied. Tests carried out for proteins of known structure indicate that the root-mean-square difference (rmsd) between the output of TALOS and the X-ray derived backbone angles is about 15s. Approximately 3% of the predictions made by TALOS are found to be in error.

J. Biomol. NMR, 13 (1999) 289-302
[PubMed PMID: 10212987]

The following table shows proteins contained in the TALOS database. Also listed are references describing the chemical shifts, the X-ray structure, the accession codes for data deposited in the BMRB and PDB databeses, the resolution at which the crystal structure was solved, and the types of nuclei for which chemical shifts are available.

Protein Chemical shifts ref. (BMRB code)	No. of residues	X-ray structure ref. (PDB code)	Resolution (Angs.)	Shifts
Alpha-lytic protease Davis et al., 1997	198	Fujinaga et al., 1985 (2alp)	1.7	C^a, C^b, C', H^a, N
Basic pancreatic trypsin inhibitor Hansen P.E., 1991	58	Wlodawer et al., 1984 (5pti)	1.1	C^a, C^b, C', H^a, N
Calbindin Drakenberg et al., 1989 (390)	76	Svensson et al., 1992 (4icb)	1.6	C^a, C^b, H^a, N
Calmodulin Ikura et al.,1990 (547)	148	Chattopadhyaya et al., 1992 (1cll)	1.7	C^a, C^b, C', H^a, N
Calmodulin/M13 Ikura et.al, 1991 (1648)	148	Meador et al., 1992 (1cdl)	2.2	C^a, C^b, C', H^a, N
Cutinase Pompers et al., 1997 (4101)	214	Longhi et al., 1997 (1cex)	1.0	C^a, C^b, C', H^a, N
Cyclophilin Ottiger et al., 1997	165	Ke, 1992 (2cpl)	1.63	C^a, C^b, H^a, N
Cyanovirin-N Bewley et al.,1998	101	Yang et al., 1999 (3ezm)	1.5	C^a, C^b, C', H^a, N
Dehydrase Copie et al., 1996	171	Leesong et al., 1996 (1mka)	2.0	C^a, C^b, C', H^a, N
D-maltodextrin-binding protein Gardner et al., 1998	370	Sharff et al., 1993 (1dmb )	1.8	C^a, C^b, C', H^a, N
HIV-1 protease Yamazaki et al., 1996	99	Lam et. al, 1994	1.8	C^a, C^b, C', H^a, N
Human carbonic anhydrase I Sethson et al., 1996 (4022)	260	Kumar and Kannan, 1994 (1hcb)	1.6	C^a, C^b, C', H^a, N
Human thioredoxin in reduced form Qin et al., 1996	105	Weichsel et al., 1996 (1ert)	1.7	C^a, C^b, H^a, N
III-glc Pelton et al., 1991	168	Worthylake et al., 1991 (1f3g)	2.1	C^a, C^b, C', H^a, N
Interleukin-1b Clore et al., 1990 (1061)	153	Veerapandian et al., 1992 (4i1b)	2.0	C^a, C^b, H^a, N
Metallo-beta-lactamase Scrofani et al., 1998 (4102)	232	Concha et al., 1996 (1znb)	1.85	C^a, C^b, C', H^a, N
Profilin Archer et. al 1994	125	Fedorov et al., 1994 (1acf)	2.0	C^a, C^b, C', H^a, N
Serine protease PB 92 Fogh et al., 1995	269	Betzel et al., 1992 (1svn)	1.4	C^a, C^b, C', H^a, N
Staph nuclease D. A. Torchia, personal communication	141	Loll and Lattman, 1989 (1snc)	1.65	C^a, C^b, C', H^a, N
Ubiquitin Wang et. al 1995	76	Vijay-Kumar et al., 1987 (1ubq)	1.8	C^a, C^b, C', H^a, N