 |
Center for Nonlinear Studies |
The folded state of a protein is described as a highly packed conformation. However, upon an increase of the hydrostatic pressure, proteins will unfold. This seems to contradict physical intuition where a low volume state is preferred at high pressures. The solution of the clue is that the unfolded state of the protein reduces the overall volume of the protein in solution by packing water molecules in the protein interior. An analysis of the potential of mean force of small non polar molecules in water supports this idea. However, the balance between energy and volume in biomolecular systems may be more complex than for simple hydrophobic solutes in water.
In my talk I will describe atomic simulations of the folding/unfolding equilibrium of a small protein and of an RNA tetraloop that exhibit pressure induced unfolding and cold denaturation. We will show that the structure and hydration of the unfolded state at low T and high P is different from the unfolded state at high T and low P. The equilibrium pressure-temperature free energy of folding, DG(P,T), is calculated from replica exchange molecular dynamics simulations. This free energy diagram has an elliptical shape, similar to what has been observed in globular proteins.
Host: Gnana Gnanakaran, T-6