The proteome: structure, function and evolution.
This paper reports two studies to model the inter-relationships between protein sequence, structure and function. First, an automated pipeline to provide a structural annotation of proteomes in the major genomes is described. The results are stored in a database at Imperial College, London (3D-GENOMICS) that can be accessed at www.sbg.bio.ic.ac.uk. Analysis of the assignments to structural superfamilies provides evolutionary insights. 3D-GENOMICS is being integrated with related proteome annotation data at University College London and the European Bioinformatics Institute in a project known as e-protein (http://www.e-protein.org/). The second topic is motivated by the developments in structural genomics projects in which the structure of a protein is determined prior to knowledge of its function. We have developed a new approach PHUNCTIONER that uses the gene ontology (GO) classification to supervise the extraction of the sequence signal responsible for protein function from a structure-based sequence alignment. Using GO we can obtain profiles for a range of specificities described in the ontology. In the region of low sequence similarity (around 15%), our method is more accurate than assignment from the closest structural homologue. The method is also able to identify the specific residues associated with the function of the protein family.
Fleming
Keiran
K
Structural Bioinformatics Group, Centre for Bioinformatics, Division of Molecular Biosciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK.
Kelley
Lawrence A
LA
Islam
Suhail A
SA
MacCallum
Robert M
RM
Muller
Arne
A
Pazos
Florencio
F
Sternberg
Michael J E
MJ
D019295:Computational Biology; D019143:Evolution, Molecular; D005810:Multigene Family; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017385:Sequence Homology
D020543:Proteome