Manual classification strategies in the ECOD database.
ECOD (Evolutionary Classification Of protein Domains) is a comprehensive and up-to-date protein structure classification database. The majority of new structures released from the PDB (Protein Data Bank) each week already have close homologs in the ECOD hierarchy and thus can be reliably partitioned into domains and classified by software without manual intervention. However, those proteins that lack confidently detectable homologs require careful analysis by experts. Although many bioinformatics resources rely on expert curation to some degree, specific examples of how this curation occurs and in what cases it is necessary are not always described. Here, we illustrate the manual classification strategy in ECOD by example, focusing on two major issues in protein classification: domain partitioning and the relationship between homology and similarity scores. Most examples show recently released and manually classified PDB structures. We discuss multi-domain proteins, discordance between sequence and structural similarities, difficulties with assessing homology with scores, and integral membrane proteins homologous to soluble proteins. By timely assimilation of newly available structures into its hierarchy, ECOD strives to provide a most accurate and updated view of the protein structure world as a result of combined computational and expert-driven analysis.
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
Hua
H
Cheng
Department of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
Yuxing
Y
Liao
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
R Dustin
RD
Schaeffer
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.|Department of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
Nick V
NV
Grishin
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D004122:Dimethylallyltranstransferase / Q000737:chemistry / Q000145:classification; D019143:Evolution, Molecular; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000145:classification; D009498:Neurotoxins / Q000737:chemistry / Q000145:classification; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012984:Software; D013111:Spider Venoms / Q000737:chemistry / Q000145:classification; D055672:Static Electricity; D009626:Terminology as Topic
D009479:Neuropeptides; D009498:Neurotoxins; D013111:Spider Venoms; C112349:TaITX-1; C101529:molt-inhibiting hormone, crayfish; D004122:Dimethylallyltranstransferase
classification; database; domain; evolution; homology; protein; sequence; structure