CONTINUOUS AND DISCONTINUOUS DOMAINS - AN ALGORITHM FOR THE AUTOMATIC-GENERATION OF RELIABLE PROTEIN DOMAIN DEFINITIONS

An algorithm is presented for the fast and accurate definition of prot ein structural domains from coordinate data without prior knowledge of the number or type of domains. The algorithm explicitly locates domai ns that comprise one or two continuous segments of protein chain. Doma ins that include more than two segments are also located. The algorith m was applied to a nonredundant database of 230 protein structures and the results compared to domain definitions obtained from the literatu re, or by inspection of the coordinates on molecular graphics. For 70% of the proteins, the derived domains agree with the reference definit ions, 18% show minor differences and only 12% (28 proteins) show very different definitions. Three screens were applied to identify the deri ved domains least likely to agree with the subjective definition set. These screens revealed a set of 173 proteins, 97% of which agree well with the subjective definitions. The algorithm represents a practical domain identification tool that can be run routinely on the entire str uctural database. Adjustment of parameters also allows smaller compact units to be identified in proteins.