Pep-Whisperer

Pep-Whisperer designs inhibitory peptides in silico to mimic and competitively bind natural partners at protein-protein interaction sites for the computational design of peptide-based inhibitors.

Key Features:

• In silico design: Performs computational design of inhibitory peptides targeting protein-protein interactions.
• Template-based approach: Generates linear peptides from templates derived from protein-protein interaction interfaces, using existing interface peptides or nonconsecutive interface residues connected by short polyalanine linkers.
• Evolutionary information integration: Incorporates evolutionary conservation of amino acids within ligand-protein binding sites to select preferred residues at each peptide position.
• Predicted binding affinity: Produces and prioritizes peptides based on predicted binding affinity to target proteins in protein complexes.
• Automation: Implements a fully automated pipeline for peptide generation and evaluation.

Scientific Applications:

• Drug discovery: Designs candidate inhibitory peptides to modulate disease-relevant protein-protein interactions.
• Therapeutic strategy exploration: Enables in silico exploration of peptide-based approaches to target complex biological pathways implicated in disease.

Methodology:

Generates linear peptides from interface-derived templates (existing interface peptides or nonconsecutive residues linked by short polyalanine linkers), incorporates evolutionary conservation of ligand-protein binding sites to select residues, and ranks peptides by predicted binding affinity.