Amide-I relaxation-induced hydrogen bond distortion: An intermediate in electron capture dissociation mass spectrometry of alpha-helical peptides?

Electron capture dissociation (ECD) of peptides and proteins in the gas phase is a powerful tool in tandem mass spectrometry whose current description is not sufficient to explain many experimental observations. Here, we attempt to bridge the current understanding of the vibrational dynamics in alpha-helices with the recent experimental results on ECD of alpha-helical peptides through consideration of amide-I relaxation-induced hydrogen bond distortion. Based on a single spine of H-bonded peptide units, we assume that charge neutralization upon electron capture by a charged alpha-helix excites a nearby amide-I mode, which relaxes over a few picoseconds due to Fermi resonances with intramolecular normal modes. The amide-I population plays the role of an external force, which drives the displacements of each peptide unit. It induces a large immobile contraction of the H bonds surrounding the excited site whose lifetime is about the amide-I lifetime. In addition, it creates two lattice deformations describing H bond stretchings, which propagate from the excited region toward both termini of the alpha-helix, get reflected at the termini and yield H bond contractions which move back to the excited region. Consequently, we show that H bonds experience rather large contractions whose amplitude depends on general features such as the position of the amide-I mode, the peptide length and the H bond force constants. When an H bond contraction is sufficiently large, it may promote a hydrogen atom transfer between two neighboring peptide units leading to the formation of a radical at charge site remote carbonyl carbon which is known to be a precursor to the rupture of the corresponding N[Single Bond]C(alpha) bond. The introduced here way of excitation energy generation and transfer may significantly advance ECD understanding and complement existing ECD mechanisms.