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PMID: 9108146 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Extracting protein alignment models from the sequence database.

Nucleic acids research ·Vol. 25 ·No. 9 ·1997-05-01 ·Pages 1665-77

Neuwald AF, Liu JS, Lipman DJ, Lawrence CE

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.

MeSH Terms
Algorithms Amino Acid Sequence Animals Bacterial Proteins/chemistry Databases, Factual GTP-Binding Proteins/chemistry Models, Chemical Molecular Sequence Data Recombinant Fusion Proteins/chemistry Sequence Alignment Sequence Homology, Amino Acid
Chemicals
Bacterial Proteins Recombinant Fusion Proteins GTP-Binding Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Neuwald A F
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. neuwald@ncbi.nlm.nih.gov
Liu J S
Lipman D J
Lawrence C E
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/25.9.1665
Email
neuwald@ncbi.nlm.nih.gov
Published
1997-05-01
Pages
1665-77
Language
English
Region
England
NLM ID
0411011
PMCID
PMC146639
Subset
IM
Grants
NHGRI NIH HHS · 1RO1-HG0125701 · United States
External Links
PubMed source DOI: 10.1093/nar/25.9.1665 PMC Full Text View journal details
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