Transitions in Chain Entanglement and Compactness Associated with in Vacuo Unfolding of Lysozyme Ions

Chain entanglement and compactness are two a priori independent properties that convey large-scale shape features of polymer conformations. In this work, we use these properties to monitor the initial step for the in vacuo unfolding of charged lysozyme ions. Using molecular dynamics simulations and a statistical model for the protein charge distribution, we show the existence of a narrow range of total charge within which compact (quasinative) and extended (partly unfolded) conformers can coexist. Denatured conformers are always found above the critical charge for unfolding, whereas quasinative structures are associated with low-charge states. We find that the global molecular shape of the accessible conformers is conserved over a range of temperatures, despite a shift in the critical charge as temperature increases. Within our model, in vacuo unfolding occurs for lysozyme ions with charges +7 and +8, when a thermal bath of T = 500 K is considered. This result is compatible with gas-phase experiments on lysozyme and suggests that unfolding results from the combined effect of heating and the Coulomb repulsion between charged residues.