Helix Positioner

Helix Positioner identifies novel single-helix binding sites within protein-protein interfaces to expand the repertoire of designable peptide ligands for modulation of PPIs.

Key Features:

• Novel Site Identification: Locates single-helix binding sites at protein-protein interfaces using structural data, including sites not utilized by native helical binders.
• Performance Validation: Validated on known single-helix-mediated PPIs by recovering key interactions and hot-spot residues characteristic of native helical binders.
• Database Screening: Screens the PDBbind database for non-helical-mediated PPIs and identified 17 potential targets suitable for helical peptide binding.
• Design and Simulation: Demonstrated design of helical peptide ligands on the L2 domain of EGFR and assessed the stability and feasibility of designed sequences using molecular dynamics simulations.

Scientific Applications:

• Therapeutic Development: Enables design of novel peptide ligands to modulate PPIs for development of therapeutic agents.
• Biological Research: Facilitates exploration of structural dynamics at protein interfaces to provide insights into mechanisms mediated by PPIs.

Methodology:

Performs structural analysis of three-dimensional protein configurations, applies predictive modeling to identify helix-compatible sites and hot-spot residues, screens PDBbind for candidate non-helical-mediated PPIs, and evaluates designed peptides by molecular dynamics simulations.