(577b) Thermodynamics and Simulation of the Negative Pressure Folding and Unfolding of Trp-Cage and GB1 Beta-Hairpin Miniproteins

Authors: 
Hatch, H. W. - Presenter, Princeton University
Debenedetti, P. G., Princeton University
Stillinger, F. H., Princeton University



Although hot, cold and high pressure denaturation are well characterized, the possibility of low and negative pressure denaturation remains virtually ignored. Proteins under negative pressure, however, are important in applications such as the effect of medical ultrasounds on proteins in the body, and the survival of proteins in the xylem and the adjacent parenchyma cells of vascular plants. In addition, low and negative pressure unfolding is fundamentally important in obtaining a complete understanding of protein stability, and naturally complements previous studies of high pressure denaturation. We use extensive REMD simulations totaling 255 microseconds to obtain folding and unfolding equilibrium for the Trp-cage miniprotien and GB1 β-hairpin in explicit water. While the Trp-cage miniprotein destabilizes at negative pressure, GB1 β-hairpin stabilizes at negative pressure. The ultimate goal is to elucidate the molecular mechanistic effect of negative pressure on protein folding and unfolding by structural analysis of the proteins and hydration water.