Kinetically Trapped Liquid-State Conformers of a Sodiated Model Peptide Observed in the Gas Phase

TL;DR

This study uses spectroscopy and simulations to explore how sodium ions influence peptide structure in the gas phase, revealing kinetically trapped conformers that differ from the most stable predicted forms.

Contribution

It demonstrates that sodium cations can kinetically trap peptide conformations in the gas phase, providing new insights into peptide-ion interactions and structural stability.

Findings

Sodiated peptides form globular structures rather than helices.

Experimentally observed structures are kinetically trapped, not the global minimum.

High energy barriers prevent re-arrangement to the lowest-energy conformers.

Abstract

We investigate the peptide AcPheAla5LysH+, a model system for studying helix formation in the gas phase, in order to fully understand the forces that stabilize the helical structure. In particular, we address the question of whether the local fixation of the positive charge at the peptide's C-terminus is a prerequisite for forming helices by replacing the protonated C-terminal Lys residue by Ala and a sodium cation. The combination of gas-phase vibrational spectroscopy of cryogenically cooled ions with molecular simulations based on density-functional theory (DFT) allows for detailed structure elucidation. For sodiated AcPheAla6, we find globular rather than helical structures, as the mobile positive charge strongly interacts with the peptide backbone and disrupts secondary structure formation. Interestingly, the global minimum structure from simulation is not present in the experiment. We interpret that this is due to high barriers involved in re-arranging the peptide-cation interaction that ultimately result in kinetically trapped structures being observed in the experiment.