Molecular dynamics (MD) simulations have been employed to address the structural changes of lysozyme (LYZ) in vacuo driven by Coulomb forces associated with multiple protonation, as occurs in electrospray ionization. Some general features which emerged from this MD study are that sufficiently high charge states drove significant unfolding and reshaping of the tertiary structure, while domain and secondary structures survived to some extent. Generally, higher charge was required to effect denaturation in comparison with experimental observations. Other physical factors not presently included in the model, viz., high internal energy, may be required to reduce the barrier for driving the unfolding process.