Test of cold denaturation mechanism for proteins as a function of water's structure

At low temperatures and high pressures (ranging from approximately 200 up to 700 MPa), some proteins become thermodynamically unstable by means of a phenomenon know as cold denaturation. A microscopic understanding of the mechanisms leading to cold denaturation is very difficult to develop, due in part to the complexity of the protein-solvent interactions. A possible proposal to explain the cold denaturation of proteins based on a relation between hydrophobicity and the loss of the local low-density water structure at high pressures is explained in detail. In the present paper, this mechanism is tested for the first time by means of full atom numerical simulations. In good agreement with the proposal, cold denaturation resulting in the unfolded state has been found at the high-density liquid (HDL) state of water, at which the amount of open tetragonal hydrogen bonds decreases at cooling.