Reflections on charge state distributions, protein structure, and the mystical mechanism of electrospray ionization

The connection between charge state distributions, protein structure, and mechanistic details of electrospray are discussed in relation to the emerging field of gas phase structural biology. Comparisons are drawn with the established area of enzymatic catalysis in organic solvents, which shares many similar challenges. Charge solvation emerges as a dominant force in both systems that must be dealt with to enable kinetic trapping of native structures in foreign environments. Potential methods for mediating unfavorable charge solvation effects are discussed and, ironically, do not include partial solvation by water. The importance of timescale in relation to the evolution of protein structure during the process of electrospray ionization is discussed. Finally several prospects for future endeavors are highlighted.