Gaseous Bradykinin and Its Singly, Doubly, and Triply Protonated Forms:  A First-Principles Study

Abstract

The conformers of gaseous bradykinin, BK, (Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)-Ser(6)-Pro(7)-Phe(8)-Arg(9)) and its protonated forms, [BK + H](+), [BK + 2H](2+), and [BK + 3H](3+), were examined theoretically using a combination of the Merck molecular force field, Hartree-Fock, and density functional theory. Neutral BK, [BK + H](+), and [BK + 2H](2+) exist in zwitterionic forms that are stabilized by internal solvation and have compact structures; [BK + 3H](3+) differs by the absence of a salt bridge and adopts an elongated form. The common structural feature in all four BK species is a beta-turn in the Ser(6)-Pro(7)-Phe(8)-Arg(9) sequence. The gas-phase basicity of [BK + H](+) estimated from the calculated protonation energy is in accord with published experimental basicity; population-weighted collision cross-sections of the three ionic forms are in agreement with experimental cross-sections in the literature.

Achieving High Resolution Ion Mobility Separations Using Traveling Waves in Compact Multiturn Structures for Lossless Ion Manipulations

“…As illustrated in Figure 4A and B, there is a minor feature (A) with a lower arrival time in addition to the major feature (B) for bradykinin, which can be attributed to another conformer, consistent with previous work. 19,54 The collision cross section of the major feature (B) was measured using drift tube IM and shown in Table 1 (the signal for the minor species was too low to obtain a reliable collision cross section). In addition, GPFRPRFPS isomer gives rise to two distinct peaks by both drift tube and TW-SLIM analyses which can be attributed to different coexisting conformers (C and D).…”

Natural structural motifs that suppress peptide ion fragmentation after electron capture

“…To avoid the lengthy process of computing and comparing the exact energies of various forms of this peptide, the zwitterion form of this peptide was taken as the predominant species based on several literature studies involving systems with similar functions. For instance, Rodriquez et al performed detailed computational analysis of gaseous bradykinin (BK) at different charge states [33]. Similar to our model peptide, BK has arginine residues (R) at both termini.…”

A density functional theory (DFT) study on gas-phase proton transfer reactions of derivatized and underivatized peptide ions generated by matrix-assisted laser desorption ionization

“…Although we cannot be sure that a complete search of the conformational space has been carried out due to the limited length of our trajectories and due to the selection of five representative snapshots, the number of snapshots selected is hampered by the need of performing DFT calculations to establish which the most stable conformer is. In fact, relative classic and DFT energies are uncorrelated and a DFT minimization is required (vide infra) [31,32].…”