Volumetric Properties of the Transition State Ensemble for Protein Folding.

Understanding how high hydrostatic pressure affects biomacromolecular interaction is important for deciphering the molecular mechanisms by which organisms adapt to live at the bottom of the ocean. The relative effect of hydrostatic pressure on the rates of folding/unfolding reactions is defined by the volumetric properties of the transition state ensemble relative to the folded and unfolded states. All-atom structure-based molecular dynamics simulations combined with quantitative computational protocol to compute volumes from three-dimensional coordinates allow volumetric mapping of protein folding landscape. This, is turn, provides qualitative understanding of the effects of hydrostatic pressure on energy landscape of proteins. The computational results for six different proteins are directly benchmark against experimental data and show an excellent agreement. Both experiments and computation show that the transition-state ensemble volume appears to be in-between the folded and unfolded state volumes, and thus the hydrostatic pressure accelerates protein unfolding.