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Abstract

The dynamic nature of intrinsically disordered peptides makes them a challenge to characterize by solution-phase techniques. In order to gain insight into the relation between the disordered state and the environment, we explore the conformational space of the N-terminal 1–5 fragment of bradykinin (BK[1–5]²⁺) in the gas phase by combining drift tube ion mobility, cold-ion spectroscopy, and first-principles simulations. The ion-mobility distribution of BK[1–5]²⁺ consists of two well-separated peaks. We demonstrate that the conformations within the peak with larger cross-section are kinetically trapped, while the more compact peak contains low-energy structures. This is a result of cis–trans isomerization of the two prolyl-peptide bonds in BK[1–5]²⁺. Density-functional theory calculations reveal that the compact structures have two very different geometries with cis–trans and trans–cis backbone conformations. Using the experimental CCSs to guide the conformational search, we find that the kinetically trapped species have a trans–trans configuration. This is consistent with NMR measurements performed in a solution, which show that 82% of the molecules adopt a trans–trans configuration and behave as a random coil.