Molecular Simulation Methods of Evaporating Electrosprayed Droplets

A robust methodology for molecular simulations of evaporating droplets that enables comparison between the dynamics of the process of interest and the solvent evaporation rate has already been developed [Oh and Consta ``Stability of a Transient Protein Complex in a Charged Aqueous Droplet with Variable pH'' J. Phys. Chem. Lett. 8, 80 (2017)]. The competition of these dynamics will determine the mass spectrum. However, the success of the approach depends on the accurate and effective treatment of electrostatic forces. Often, in droplet simulations, bulk solution parametrized force-fields are used where the Coulomb forces are directly taken into account with a cut-off distance longer than the droplet diameter. On the one hand this approach is inefficient for large droplets because the computational cost increases as the squared of the number of the atomic sites, and on the other hand the force field is not the same as that that has been parametrized for the bulk solution. The effect of this new force field in the conformations of macromolecules is still unknown. Multilevel summation method (MSM) has been developed [Hardy et al. ``Multilevel summation method for electrostatic force evaluation'' J. Chem. Theory Comput. 11, 766 (2015)] for the efficient treatment of electrostatic forces in non-periodic and semi-periodic systems, charged or neutral. MSM maintains the same force field in droplets as in the bulk solution. We compare MSM with direct electrostatic treatment in droplets. The comparison shows the same probability distribution of the conformations, but differences in the rate of transition between the conformations. We demonstrate the usage MSM to study Rayleigh jet formation and charge emission from droplets. We conclude that robust approaches for droplet simulations that can be used with a force field of any complexity are available and can be implemented within many of the available open-source molecular modeling softwares. In the near future, the presented approach may provide reliable reference mass spectra for experiments, where the deviations from the experimental data may reveal valuable information about the processes that take place within the instrument.