Computer-assisted assignment of multidimensional NMR spectra of proteins: Application to 3D NOESY-HMQC and TOCSY-HMQC spectra

✍ Scribed by Reimond Bernstein; Christian Cieslar; Alfred Ross; Hartmut Oschkinat; Jens Freund; Tad A. Holak

• Publisher: Springer Netherlands
• Year: 1993
• Tongue: English
• Weight: 418 KB
• Volume: 3
• Category: Article
• ISSN: 0925-2738
• DOI: 10.1007/bf00178267

✦ Synopsis

An algorithm based on the technique of combinatorial minimization is used for the semi-automated assignment of multidimensional heteronuclear spectra. The program (ALFA) produces the best assignment compatible with the available input data. Even partially misleading or missing data do not seriously corrupt the final assignment. Ambiguous sequences of the possible assignment and all alternatives are indicated. The program can also use additional non-spectroscopic data to assist in the assignment procedure. For example, information from the X-ray structure of the protein and/or information about the secondary structure can be used. The assignment procedure was tested on spectra of mucous trypsin inhibitor, a protein of 107 residues.

The assignment of multidimensional spectra of macromolecules is still the bottleneck in structure determination by NMR (Wiithrich et al., 1982;Eccles et al., 1991;Kleywegt et al., 1991). There are a number of reasons why this procedure has resisted automation: all spectra contain noise and artifacts, and the list of spin systems and their peaks are often incomplete due to spectral overlap and internal motion. The characterization of the type of the spin system is far from unique (