Title
Functional Coverage Of The Human Genome By Existing Structures, Structural Genomics Targets, And Homology Models
Abstract
The bias in protein structure and function space resulting from experimental limitations and targeting of particular functional classes of proteins by structural biologists has long been recognized, but never continuously quantified. Using the Enzyme Commission and the Gene Ontology classifications as a reference frame, and integrating structure data from the Protein Data Bank (PDB), target sequences from the structural genomics projects, structure homology derived from the SUPERFAMILY database, and genome annotations from Ensembl and NCBI, we provide a quantified view, both at the domain and whole-protein levels, of the current and projected coverage of protein structure and function space relative to the human genome. Protein structures currently provide at least one domain that covers 37% of the functional classes identified in the genome; whole structure coverage exists for 25% of the genome. If all the structural genomics targets were solved (twice the current number of structures in the PDB), it is estimated that structures of one domain would cover 69% of the functional classes identified and complete structure coverage would be 44%. Homology models from existing experimental structures extend the 37% coverage to 56% of the genome as single domains and 25% to 31% for complete structures. Coverage from homology models is not evenly distributed by protein family, reflecting differing degrees of sequence and structure divergence within families. While these data provide coverage, conversely, they also systematically highlight functional classes of proteins for which structures should be determined. Current key functional families without structure representation are highlighted here; updated information on the "most wanted list" that should be solved is available on a weekly basis from http://function.rcsb. org:8080/pdb/function-distribution/index.html..
Year
DOI
Venue
2005
10.1371/journal.pcbi.0010031
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
protein family,structural genomics,indexation,function space,human genome,protein structure,genome annotation,reference frame,structured data,single domain,protein data bank,homology modeling
Genome,Protein family,Protein domain,Structural genomics,Biology,Ensembl,Genomics,Bioinformatics,Protein Data Bank,Genetics,Protein Data Bank (RCSB PDB)
Journal
Volume
Issue
ISSN
1
3
1553-734X
Citations 
PageRank 
References 
24
3.99
14
Authors
2
Name
Order
Citations
PageRank
Lei Xie144139.48
Philip E. Bourne21995388.17