ECOD in 2027: a modernized interface and an updated classification of protein domains

The Evolutionary Classification of Domains (ECOD) organizes protein domains into a hierarchy of evolutionary relationships, encompassing both experimentally determined and computationally predicted structures. ECOD now classifies 2.9M domains, of which ∼1.37M derived from the Protein Data Bank and 1.51M from predicted models in the AlphaFold Protein Structure Database. The principal development we report here is a complete rebuild of the ECOD web resource. Search has been reconstructed around three modalities: (i) sequence, (ii) structure, and (iii) keyword. Foldseek now is the primary search method for the ECOD web page, searching a ∼457k representative domain database that is also distributed for local use. Results are presented through a Mol* interactive viewer, and a new API has been developed for programmatic access to the database. Alongside the interface, the pipeline for classifying new PDB entries has been rebuilt and returned to a regular cadence, family groups have been synchronized with Pfam v38.2, the bulk distributables have been reorganized and now include the search databases, the ligands in contact with each domain are recorded for experimental structures and annotated with drug cross-references from DrugDomain, and a registry has been introduced through which ECOD assigns stable identifiers to gene-called proteins and records the structures it predicts. ECOD is freely available at http://prodata.swmed.edu/ecod.