Download Nick Grishin "Evolutionary Classification of Protein Domains

Nick Grishin
"Evolutionary Classification of Protein Domains."
Evolutionary relationships (i.e., homology) detected between proteins helps predict their properties
such as spatial structures and functions.
Homology is frequently obscured by sequence divergence, spatial structure changes and resemblance
between unrelated 3D structures. We have developed a hierarchical evolutionary classification of all
proteins with experimentally determined spatial structures. 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"). 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, all 120,000 protein structures from
PDB are classified in ECOD into 13,000 sequence families clustered into 3,000 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.