HighDB: New structure-annotated cyclic peptide database offers 2,504 entries for design and analysis

Cyclic peptides are increasingly recognized as potent modulators for challenging drug targets and protein-protein interactions (PPIs), offering unique structural and functional advantages over linear counterparts. Despite their therapeutic promise, the design and optimization of target-specific cyclic peptides are significantly hampered by a scarcity of comprehensive, structure-centered resources. Existing databases often lack standardized, computable annotations and sufficient depth in experimentally resolved structures, creating a critical gap for researchers seeking to leverage these complex molecules in drug discovery and bioengineering.

Researchers developed HighDB, a curated database of experimentally resolved cyclic peptide structures. Data was collected from the Protein Data Bank (PDB) and relevant literature, with each entry annotated at the PDB-chain level. The team harmonized annotations across key descriptors including cyclization type, ring number, overall secondary structure, peptide naturalness, and complex context. HighDB integrates multiple functionalities such as keyword retrieval, multidimensional filtering, sequence-similarity search, and interactive three-dimensional visualization to facilitate structural analysis and design-oriented applications. They also established a unified annotation framework for topological and conformational descriptors.

HighDB's current release contains 2,504 entries, each meticulously annotated at the PDB-chain level. This collection is harmonized across crucial parameters like cyclization type, ring number, overall secondary structure, peptide naturalness, and complex context. The database offers robust functionalities including keyword retrieval, multidimensional filtering, sequence-similarity search, and interactive three-dimensional visualization, supporting diverse applications from comparative structural analysis to template retrieval and design-oriented exploration. Comparative analysis with other representative cyclic peptide resources demonstrated that HighDB provides broader annotation coverage and boasts the largest collection of experimentally resolved cyclic peptide structures among the databases examined. This comprehensive resource is freely accessible for academic use.

HighDB currently contains 2,504 entries, annotated at the PDB-chain level, representing the largest collection of experimentally resolved cyclic peptide structures among the databases examined.