USE OF GRAPH-THEORY FOR SECONDARY STRUCTURE RECOGNITION AND SEQUENTIAL ASSIGNMENT IN HETERONUCLEAR (C-13, N-15) NMR-SPECTRA - APPLICATION TO HU PROTEIN FROM BACILLUS-STEAROTHERMOPHILUS
Ec. Vangeeresteinujah et al., USE OF GRAPH-THEORY FOR SECONDARY STRUCTURE RECOGNITION AND SEQUENTIAL ASSIGNMENT IN HETERONUCLEAR (C-13, N-15) NMR-SPECTRA - APPLICATION TO HU PROTEIN FROM BACILLUS-STEAROTHERMOPHILUS, Biopolymers, 39(5), 1996, pp. 691-707
A computer-assisted procedure, based upon a branch of mathematics know
n as graph theory, has been developed to recognize secondary structure
elements in proteins from their corresponding nuclear Overhauser effe
ct spectroscopy (NOESY)-type spectra and to carry out their sequential
assignment. In the method, NOE connectivity templates characteristic
of regular secondary structures are identified in the spectra. Resonan
ce assignment is then achieved by connecting these NOE patterns of sec
ondary structure together, and thereby matching connected spin systems
to specific pacts of the primary sequence. The range of NOE-graph tem
plates of secondary structure motifs, incorporating alpha-helices and
beta-strand motifs, has been examined for reliability and extent of se
condary structure identification in a data base composed of the high r
esolution structures of 20 proteins. The analysis identified several r
obust NOE-graph templates and supports the implementation of an ordere
d search strategy. The method, known as SERENDIPITY, has been applied
to the analysis of nuclear Overhauser effect data from a three-dimensi
onal time-shared nuclear Overhauser effect spectroscopy (C-13, N-15) h
eteronuclear single quantum correlation spectrum of the (alpha + beta)
type protein HU from Bacillus stearothermophilus. The arrangement of
the elucidated elements of secondary structure is very similar to that
of the x-ray and nmr structures of HU. In addition, our analysis reve
aled a pattern of interstrand nuclear Overhauser effect in the beta-ar
m region (residues 53-76) of HU, which suggest irregularities, not rep
orted in the x-ray structure, in both strands of the beta-arm at Ala57
and Pro72, respectively. At these residues, both strands of the beta-
arm appear to flip inside out before continuing as a regular antiparal
lel beta-sheet. (C) 1996 John Wiley & Sons, Inc.