Helix unfolding in unsolvated peptides

Area of Science:

• Chemical Physics
• Biophysical Chemistry
• Molecular Dynamics

Background:

• Understanding peptide structure is crucial for biological function.
• Peptide conformations can be influenced by sequence and environment.
• Ion mobility is a powerful technique for studying gas-phase peptide structures.

Purpose of the Study:

• To investigate the temperature-dependent conformations of two specific peptides: Ac-K(AGG)(5)+H(+) and Ac-(AGG)(5)K+H(+).
• To characterize the unfolding pathways and kinetics of helical peptide structures.
• To identify potential intermediate conformations during peptide unfolding.

Main Methods:

• Ion mobility measurements were performed over a wide temperature range (150-410 K).
• Kinetic analysis of helix unfolding was conducted using rate constants.
• Molecular dynamics simulations were employed to explore conformational landscapes.

Main Results:

• The Ac-K(AGG)(5)+H(+) peptide maintained a globule conformation across all tested temperatures.
• The Ac-(AGG)(5)K+H(+) peptide exhibited both alpha-helix and globule forms at low temperatures.
• Alpha-helix unfolding occurred on a millisecond timescale, yielding an activation energy of 38.2 kJ/mol.
• A long-lived intermediate conformation was observed between the helix and globule states.

Conclusions:

• Peptide Ac-K(AGG)(5)+H(+) is conformationally stable as a globule.
• Peptide Ac-(AGG)(5)K+H(+) undergoes temperature-induced unfolding from an alpha-helix.
• A distinct, stable intermediate structure likely facilitates the transition from helix to globule.
• Molecular dynamics simulations support the existence of this intermediate as a partially untwisted helix.