Self-binding peptides: Binding-upon-folding versus folding-upon-binding.

Area of Science:

• Biomolecular dynamics
• Protein folding and binding interactions
• Molecular biophysics

Background:

• Self-binding peptides (SBPs) are short, structurally independent peptide segments within monomeric proteins.
• SBPs fulfill biological functions through dynamic binding and unbinding to target domains within the same monomer.
• This phenomenon bridges the gap between protein folding and molecular binding.

Purpose of the Study:

• To systematically investigate the behavior of four representative Self-binding peptide systems.
• To compare the native bound, unbound, and isolated states of Self-binding peptide moieties.
• To elucidate the mechanism and factors influencing Self-binding peptide interactions.

Main Methods:

• Atomistic molecular dynamics (MD) simulations were employed.
• Post-binding energetics analyses were conducted.
• Comparative analysis of different structural states (bound, unbound, isolated) was performed.

Main Results:

• Self-binding peptide interaction with targets is primarily a single-molecule binding phenomenon.
• A polypeptide linker between the Self-binding peptide and its target can enhance binding efficiency.
• Linker-induced proximity statistically increases the probability of Self-binding peptide-target encounters.

Conclusions:

• Self-binding peptides exhibit a novel biological event termed 'binding-upon-folding'.
• This contrasts with the classical 'folding-upon-binding' mechanism observed in other peptide interactions.
• The findings propose a new paradigm for understanding peptide-protein interactions and molecular recognition.