From the solution to the gas phase: A numerical experiment on the electrospray process of triprotonated Bradykinin

Molecular Dynamics simulations in conjunction with principal component analysis have been used to model the processes underlying electrospray (ESI) and ion-mobility mass spectrometry (IMMS) experiments. The triprotonated Bradykinin (BK3+) has been selected as a case study. Our results have shown that the conformational features of solvated BK3+ are essentially maintained during the whole process of droplet evaporation. On the other hand these features result partially lost during the motion of the peptide inside the drift tube where the relative cis-trans stability of the prolyl-peptide bonds turns out to be significantly different from the solution state where all-trans isomers have been systematically found. Collision cross sections (CCS) calculated on the BK3+ gaseous population appear as strongly correlated to the shape of BK3+, in particular its length, which on the other hand is scarcely dependent on the prolyl-peptide bond configuration. This finding suggests that in correspondence of a single IMMS peak, different BK3+ conformers characterized by similar shape can be present. The limitations of a computational modeling at atomistic level of this kind of experiments have been discussed. As a matter of fact our study has only partially reproduced the experimental data: while the position of the peaks, i.e. the values of the calculated CCS, have been reproduced with rather good agreement, the assignment of the various cis–trans conformational states of the prolyl-peptide bond revealed not correct if compared to experimental data. This latter disagreement has been considered to be mainly due to the free energy differences between the various conformational states, resulted rather small and hence not fully captured by the empirical force fields.