Folded-State Compatibility and Unfolded-State Constraint Govern Staple-Based Stabilization: Guidelines from a Coiled-Coil Model

Key Points

• The research aims to establish guidelines for selecting staple sites in peptide stapling to improve protein stability and functionality.
• Utilized a coiled-coil model to examine protein conformational stability.
• Analyzed the effects of staple positioning on proteolytic resistance.
• Evaluated biomolecular recognition metrics to assess effectiveness.
• Identified key principles for selecting staple sites that enhance protein stability.
• Demonstrated improved resistance against proteolysis with optimal staple designs.
• Showed that appropriate stabilization significantly boosts biomolecular recognition.