title: Extracting protein alignment models from the sequence database.
abstract: Biologists often gain structural and functional insights into a protein sequence by constructing a multiple alignment model of the family. Here a program called Probe fully automates this process of model construction starting from a single sequence. Central to this program is a powerful new method to locate and align only those, often subtly, conserved patterns essential to the family as a whole. When applied to randomly 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 Caenorhabditis 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 distant relationships and merging families into superfamilies in this way, this analysis further confirms the notion that proteins evolved from relatively few ancient sequences. Moreover, this method automatically generates models of these ancient conserved regions for rapid and sensitive screening of sequences.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. neuwald@ncbi.nlm.nih.gov
authors.forename: A F
authors.initials: AF
authors.lastname: Neuwald
authors.forename: J S
authors.initials: JS
authors.lastname: Liu
authors.forename: D J
authors.initials: DJ
authors.lastname: Lipman
authors.forename: C E
authors.initials: CE
authors.lastname: Lawrence
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D016208:Databases, Factual; D019204:GTP-Binding Proteins / Q000737:chemistry; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D011993:Recombinant Fusion Proteins; D019204:GTP-Binding Proteins