Molecular Dynamics Simulations of Charged Nanodroplets

Charged nanodroplets represent a fascinating research area due to their unique dynamics and physical properties. These nanodroplets play a key role in electrospray mass spectrometry (ESI-MS), which is a method for analyzing organic/inorganic molecules as well as proteins and other biomolecular species. The mechanism whereby these analytes are transferred into the gas phase as intact ions remains incompletely understood. Two competing models have been proposed to explain the process, the charged residue model (CRM) and the ion evaporation model (IEM). Under the CRM, evaporation of the droplet proceeds until dryness, at which point the analyte ion is left behind. Under the IEM model, analyte ions are released from the droplet surface by overcoming an activation energy barrier. In this work, molecular dynamics (MD) simulations were used with the goal of characterizing the nanodroplet behavior in more detail, and for gaining insights in the mechanism of gas phase ion formation during ESI. Three atom site models were used to represent water as well as methanol. The droplets contained 1000 – 1500 solvent molecules, providing radii of ~ 18 – 23 Å. Excess charge was accounted for by including protons, sodium and ammonium ions. A number of investigations were conducted by including a coarse-grained model protein in the droplet. Different protein conformations (unfolded and folded) were investigated with hydrophobic or hydrophilic side chain patterns. As part of the findings of this work, it was discovered that ion location and charge location within the droplets do not coincide. Instead, water dipole orientation projects the charge from the interior to the droplet surface. The observed behavior helps resolve an apparent conundrum in the existing ESI literature. Small ions were shown to undergo ejection events that are consistent with an IEM type scenario. Unfolded hydrophobic protein chains also display a behavior reminiscent of the IEM, while folded and hydrophilic unfolded versions show CRM characteristics. Overall the results of this thesis contribute to a better understanding of the nanodroplet behavior by shedding light on the final stages of the ESI process