Determining the gas-phase structures of α-helical peptides from shape, microsolvation, and intramolecular distance data.

Wu, Ri; Metternich, Jonas B.; Kamenik, Anna S.; Tiwari, Prince; Harrison, Julian A.; Kessen, Dennis; Akay, Hasan; Benzenberg, Lukas R.; Chan, T.-W. Dominic; Riniker, Sereina; Zenobi, Renato

Mass spectrometry is a powerful technique for the structural and functional characterization of biomolecules. However, it remains challenging to accurately gauge the gas-phase structure of biomolecular ions and assess to what extent native-like structures are maintained. Here we propose a synergistic approach which utilizes Förster resonance energy transfer and two types of ion mobility spectrometry (i.e., traveling wave and differential) to provide multiple constraints (i.e., shape and intramolecular distance) for structure-refinement of gas-phase ions. We add microsolvation calculations to assess the interaction sites and energies between the biomolecular ions and gaseous additives. This combined strategy is employed to distinguish conformers and understand the gas-phase structures of two isomeric α-helical peptides that might differ in helicity. Our work allows more stringent structural characterization of biologically relevant molecules (e.g., peptide drugs) and large biomolecular ions than using only a single structural methodology in the gas phase. It remains challenging to gauge the gas-phase structure of biomolecular ions and assess to what extent native-like structures are maintained. Here, the authors utilize Förster resonance energy transfer and ion mobility spectrometry for more stringent structural characterization of biomolecular ions.

FLUORESCENCE resonance energy transfer; ION mobility spectroscopy; SOLVATION; IONIC structure; PEPTIDES; ION energy; MASS spectrometry

Nature Communications, 2023, Vol 14, Issue 1, p1

2041-1723

Academic Journal

10.1038/s41467-023-38463-z