TEDLH: domain HMMs for sensitive detection of remote homologues.

TEDLH links nearly one million protein domain HMMs to structural data, expanding detection of remote homologues and revealing evolutionary relationships across protein families.

• Why it matters: Understanding distant protein homologies is crucial for accurate annotation and functional prediction, yet existing methods often lack sensitivity for divergent sequences, creating gaps in evolutionary knowledge.
• What they did: Constructed from AlphaFold protein annotations, TEDLH comprises 934,186 domain HMMs connected to CATH-PDB structures through direct and transitive relationships, enhancing coverage of divergent regions and superfamily diversity.
• The result: This approach improves detection of structurally similar but sequence-divergent proteins, offers insights into evolutionary links between superfamilies, and supports systematic exploration of protein domain evolution.