Molecular Simulation Methods of Evaporating Electrosprayed Droplets

Molecular simulations provide considerable insight in elucidating the relation between the release of a macromolecule from charged droplets and its charge state, and in determining possible location of the charge in macroions detected by mass spectrometry. However, there is a number of significant challenges to consider in the modeling. These challenges include the effect of the droplet-size dependent chemistry in the charge state of a macroion, limitations in force fields, performance of efficient droplet evaporation at any temperature, and efficient treatment of the electrostatic interactions. Here, we present a robust methodology for molecular simulations that allows for the study of the chemistry and interactions of macromolecules within a droplet, and the relation of the dynamics of the process of interest to the solvent evaporation rate. The competition of these dynamical processes will determine the mass spectrum. We discuss the simulation setup and the treatment of the electrostatic interactions. Multilevel summation method (MSM) has been developed [Hardy et al. ``Multilevel summation method for electrostatic force evaluation'' J. Chem. Theory Comput. {\bf 11}, 766 (2015)] for the efficient treatment of electrostatics in non-periodic and semi-periodic systems, charged and neutral. We present comparison of MSM with particle-mesh Ewald (PME) method in order to show MSM's ability to study conformational changes of macromolecules in droplets. We demonstrate the capability of spherical boundary condition and MSM in the studies of physical and chemical process in droplets by using the example of the Rayleigh jet formation and charge emission from it.