EXTRACTING PROTEIN ALIGNMENT MODELS FROM THE SEQUENCE DATABASE

Biologists often gain structural and functional insights into a protei n sequence by constructing a multiple alignment model of the family. H ere a program called PROBE fully automates this process of model const ruction starting from a single sequence. Central to this program is a powerful new method to locate and align only those, often subtly, cons erved patterns essential to the family as a whole. When applied to ran domly chosen proteins, PROBE found on average about four times as many relationships as a pairwise search and yielded many new discoveries, These include: an obscure subfamily of globins in the roundworm Caenor habditis elegans; two new superfamilies of metallohydrolases; a lipoyl /biotin swinging arm domain in bacterial membrane fusion proteins; and a DH domain in the yeast Bud3 and Fus2 proteins. By identifying dista nt relationships and merging families into superfamilies in this way, this analysis further confirms the notion that proteins evolved from r elatively few ancient sequences, Moreover, this method automatically g enerates models of these ancient conserved regions for rapid and sensi tive screening of sequences.