Monitorying the Desolvaiton of Ions and Create Candidate Structure for the Ions Detected by Ion Mobility-Mass Spectrometry Study by Molecular Dynamics Simulations

Abstract

Electrospray ionization ion mobility mass spectrometry (ESI-IM-MS) has emerged in recent years as a tool to separate heterogeneous conformer populations and determine ion-neutral collision cross sections (CCS). However, IM cannot provide specific structural information such as atomic coordinates obtained from X-ray crystallography or nuclear magnetic resonance (NMR) experiments. In this work, molecular dynamics simulations (MDS), and quantum mechanical simulations were used to provide structural information for three families of peptides previously characterized by IM: substance P (SP) and its mutants, phosphopeptides with various phosphorylation locations and mutants, and polyprolines. The simulated structure’s theoretical CCS was calculated by using the MOBCAL trajectory method. CCS values from ESI-IM-MS experiments provided boundary conditions to filter simulated structures to within ±3% of experimental CCS values. Additional experimental results, such as electron capture dissociation (ECD) and proline cis/trans conformation results, were also used to filter simulated structures which enhanced further the validity of simulated structure.

The electrospray process was also investigated by utilizing MDS for the ultimate goal to understand the structure evolution of ions from solution to the gas phase. A series of conditioning simulations determined the optimum droplet size to be ~2400 water molecules, and the temperature of desolvation simulation was determined to be 360 K, which is consistent with the previously reported ESI-cryo-IM-MS heated capillary temperature. The net charge of the droplet was determined to be +15. Using these determined conditions, three desolvation simulations were performed with SP as model. The desolvation results showed evaporation and droplet fission which were consistent with other simulations. A further desolvation study incorporated Cl- in the droplet containing SP3+ as counter ions. The structural evolution of the SP3+ ion during the desolvation process was monitored via CCS calculations. The calculated CCS of the SP3+ ion during the later stages of desolvation was consistent with the previously determined ESI-IM-MS value. This simulation indicates that the droplet desolvation follows the process best described as the combined charge residue-field emission model.