Helical structure motifs made searchable for functional peptide design

The systematic design of functional peptides has technological and therapeutic applications.
However, there is a need for pattern-based search engines that help locate desired functional
motifs in primary sequences regardless of their evolutionary conservation. Existing databases
such as The Protein Secondary Structure database (PSS) no longer serves the community,
while the Dictionary of Protein Secondary Structure (DSSP) annotates the secondary
structures when tertiary structures of proteins are provided. Here, we extract 1.7 million
helices from the PDB and compile them into a database (Therapeutic Peptide Design database; TP-DB) that allows queries of compounded patterns to facilitate the identification of
sequence motifs of helical structures. We show how TP-DB helps us identify a known
purification-tag-specific antibody that can be repurposed into a diagnostic kit for Helicobacter
pylori. We also show how the database can be used to design a new antimicrobial peptide
that shows better Candida albicans clearance and lower hemolysis than its template homologs. Finally, we demonstrate how TP-DB can suggest point mutations in helical peptide
blockers to prevent a targeted tumorigenic protein-protein interaction. TP-DB is made
available at http://dyn.life.nthu.edu.tw/design/.