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ECOD: an evolutionary classification of protein domains.

Cheng H, Schaeffer RD, Liao Y, Kinch LN, Pei J, Shi S, Kim BH, Grishin NV - PLoS Comput. Biol. (2014)

Bottom Line: The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates.This synchronization with PDB uniquely distinguishes ECOD among all protein classifications.Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.

ABSTRACT
Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or "fold"). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.

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A) Distribution of domains per chain for ECOD(red), SCOP(green), and CATH(blue).Both ECOD and SCOP allow for multi-chain domains (MC), but these are a small fraction of the classification. ECOD contains slightly more single-chain domains than CATH, but less than SCOP. B) ECOD slightly favors smaller domains over SCOP and longer domains over CATH.
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pcbi-1003926-g008: A) Distribution of domains per chain for ECOD(red), SCOP(green), and CATH(blue).Both ECOD and SCOP allow for multi-chain domains (MC), but these are a small fraction of the classification. ECOD contains slightly more single-chain domains than CATH, but less than SCOP. B) ECOD slightly favors smaller domains over SCOP and longer domains over CATH.

Mentions: We compared the domain partition observed in ECOD, SCOP, and CATH. Domain partition strategy can differ markedly between classifications, depending generally on whether the presence of compact structural units or overall sequence similarity is emphasized. The number of domains per chain observed in the domain classifications is presented in Figure 8(a). ECOD splits more protein chains (29%) into multiple domains than SCOP (23%), but splits slightly less than CATH (35%). The size distribution of domains in ECOD, SCOP, and CATH was compared (Fig. 8(b)). ECOD favors slightly shorter domains than SCOP, and favors slightly longer domains over CATH, but the size distributions are very similar. These results are consistent with the differences in domain definition strategy employed by different classifications. CATH emphasizes on structural integrity of the domain and its structural separation from other domains, SCOP focuses on the occurrence of an individual domain in different domain combinations, and ECOD attempts to find a compromise between these two strategies.


ECOD: an evolutionary classification of protein domains.

Cheng H, Schaeffer RD, Liao Y, Kinch LN, Pei J, Shi S, Kim BH, Grishin NV - PLoS Comput. Biol. (2014)

A) Distribution of domains per chain for ECOD(red), SCOP(green), and CATH(blue).Both ECOD and SCOP allow for multi-chain domains (MC), but these are a small fraction of the classification. ECOD contains slightly more single-chain domains than CATH, but less than SCOP. B) ECOD slightly favors smaller domains over SCOP and longer domains over CATH.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256011&req=5

pcbi-1003926-g008: A) Distribution of domains per chain for ECOD(red), SCOP(green), and CATH(blue).Both ECOD and SCOP allow for multi-chain domains (MC), but these are a small fraction of the classification. ECOD contains slightly more single-chain domains than CATH, but less than SCOP. B) ECOD slightly favors smaller domains over SCOP and longer domains over CATH.
Mentions: We compared the domain partition observed in ECOD, SCOP, and CATH. Domain partition strategy can differ markedly between classifications, depending generally on whether the presence of compact structural units or overall sequence similarity is emphasized. The number of domains per chain observed in the domain classifications is presented in Figure 8(a). ECOD splits more protein chains (29%) into multiple domains than SCOP (23%), but splits slightly less than CATH (35%). The size distribution of domains in ECOD, SCOP, and CATH was compared (Fig. 8(b)). ECOD favors slightly shorter domains than SCOP, and favors slightly longer domains over CATH, but the size distributions are very similar. These results are consistent with the differences in domain definition strategy employed by different classifications. CATH emphasizes on structural integrity of the domain and its structural separation from other domains, SCOP focuses on the occurrence of an individual domain in different domain combinations, and ECOD attempts to find a compromise between these two strategies.

Bottom Line: The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates.This synchronization with PDB uniquely distinguishes ECOD among all protein classifications.Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.

ABSTRACT
Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or "fold"). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.

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