Sequence-specific NMR assignment of proteins by global fragment mapping with the program MAPPER

A new program, Mapper, for semiautomatic sequence-specific NMR assignment i n proteins is introduced. The program uses an input of short fragments of s equentially neighboring residues, which have been assembled based on sequen tial NMR connectivities and for which either the C-13(alpha) and C-13(beta) chemical shifts or data on the amino acid type from other sources are know n. Mapper then performs an exhaustive search for self-consistent simultaneo us mappings of all these fragments onto the protein sequence. Compared to u sing only the individual mappings of the spectroscopically connected fragme nts, the global mapping adds a powerful new constraint, which results in re solving many otherwise intractable ambiguities. In an initial application, virtually complete sequence-specific assignments were obtained for a 110 kD a homooctameric protein, 7,8-dihydroneopterin aldolase from Staphylococcus aureus.