TP-DB

TP-DB provides a searchable database of α-helical peptide sequences extracted from the Protein Data Bank (PDB) to support structure-based design of therapeutic peptides and diagnostic reagents.

Key Features:

• Extensive database: Nearly 1.7 million α-helical peptide sequences extracted from over 130,000 proteins in the Protein Data Bank (PDB) are compiled and indexed.
• Pattern-based search engine: A search engine that identifies specific sequence motifs without relying on evolutionary homology, contrasted with PHI-BLAST.
• Pattern and gap indexing: Sequences are indexed with explicit patterns and gaps to enable intricate searches for spaced residue motifs.
• Secondary-structure focus: Emphasis on α-helices and their physicochemical sequence motifs relevant to peptide function and design.

Scientific Applications:

• Pathogen identification and diagnostic repurposing: Identification of the DYKYLE motif in Helicobacter pylori neutrophil-activating protein (HP-NAP) enabled repurposing of anti-FLAG M2 antibodies for diagnostic use.
• Antimicrobial peptide design: Discovery of membrane-insertion patterns such as WXXWXXW guided synthesis of antimicrobial peptides with improved efficacy and reduced cytotoxicity against Candida albicans.
• Cancer research: Identification and analysis of helical peptides involved in helix-helix interactions relevant to hepatocellular carcinoma, with helicity and binding affinity assessed by molecular dynamics (MD) simulations.

Methodology:

Extraction of nearly 1.7 million α-helical peptide sequences from over 130,000 PDB proteins; indexing sequences with explicit patterns and gaps; a pattern-based search engine for motif identification without inferring evolutionary homology; and molecular dynamics (MD) simulations to evaluate helicity and binding affinity.