Helical structure motifs made searchable for functional peptide design

Area of Science:

• Biotechnology
• Computational Biology
• Peptide Science

Background:

• Designing functional peptides for technological and therapeutic use requires efficient methods to identify sequence motifs.
• Existing databases have limitations in pattern-based searching of functional motifs irrespective of evolutionary conservation.
• The Protein Secondary Structure database is outdated, and the Dictionary of Protein Secondary Structure requires tertiary structures for annotation.

Purpose of the Study:

• To develop a pattern-based search engine for identifying functional motifs in peptide sequences.
• To create a comprehensive database of helical structures for peptide design applications.
• To demonstrate the utility of the database in repurposing antibodies, designing antimicrobial peptides, and engineering peptide blockers.

Main Methods:

• Extraction of 1.7 million helices from the Protein Data Bank (PDB).
• Compilation of extracted helices into the Therapeutic Peptide Design database (TP-DB).
• Development of query functionalities for compounded patterns within helical structures.

Main Results:

• TP-DB enables the identification of a purification-tag-specific antibody for repurposing into a diagnostic kit for Helicobacter pylori.
• The database facilitated the design of a novel antimicrobial peptide with enhanced Candida albicans clearance and reduced hemolysis compared to homologs.
• TP-DB provided insights for designing point mutations in helical peptide blockers to inhibit a specific tumorigenic protein-protein interaction.

Conclusions:

• The Therapeutic Peptide Design database (TP-DB) is a valuable resource for identifying and designing functional peptides.
• TP-DB supports diverse applications, including diagnostics, antimicrobial peptide development, and protein-protein interaction modulation.
• The database is accessible online at http://dyn.life.nthu.edu.tw/design/ for broader scientific use.