Proteins in vacuo: A molecular dynamics study of the unfolding behavior ofhighly charged disulfide-bond-intact lysozyme subjected to a temperature pulse

Molecular dynamics simulations were used to interpret a variety of experime ntal data on highly charged disulfide-bond-intact lysozyme in vacuo. The si mulation approach involved submitting a model of the protein [Reimann, Vela zquez, and Tapia, J. Phys. Chem. B 102, 9344 (1998)] in a given charge stat e to a 3-ns-long heat pulse (usually at 500 K) followed by cooling or relax ation for 1 ns back to room temperature (293 K). This treatment yielded a c harge threshold around Q(0)=8+ for obtaining significant unfolding, as indi cated by an enhancement in collision cross section and conformer length. Th e collision cross sections and lengths theoretically obtained, along with t he threshold charge state for initiating unfolding, were compatible with ex perimental results on lysozyme in vacuo. The unfolded, highly elongated con formations obtained for Q greater than or equal to 9+ displayed a significa nt level of non-native beta-sheet content which appeared to be additionally stabilized by charge self-solvation. [S1063-651X(99)06312-6].