In order to investigate the cryoprotective mechanism of trehalose on proteins, we use molecular dynamics computer simulations to study the microscopic dynamics of water upon cooling in an aqueous solution of lysozyme and trehalose. We find that the presence of trehalose causes global retardation of the dynamics of water. Comparing aqueous solutions of lysozyme with/without trehalose, we observe that the dynamics of water in the hydration layers close to the protein is dramatically slower when trehalose is present in the system. We also analyze the structure of water and trehalose around the lysozyme and find that the trehalose molecules form a cage surrounding the protein that contains very slow water molecules. We conclude that the transient cage of trehalose molecules that entraps and slows the water molecules prevents the crystallisation of protein hydration water upon cooling.

Using Wolff's cluster Monte Carlo simulations and numerical minimization within a mean field approach, we study the low temperature phase diagram of water, adopting a cell model that reproduces the known properties of water in its fluid phases. Both methods allow us to study the thermodynamic behavior of water at temperatures, where other numerical approaches -both Monte Carlo and molecular dynamics -are seriously hampered by the large increase of the correlation times. The cluster algorithm also allows us to emphasize that the liquid-liquid phase transition corresponds to the percolation transition of tetrahedrally ordered water molecules.Published by Elsevier B.V.

Using Monte Carlo simulations we study a coarse-grained model of a water layer confined in a fixed disordered matrix of hydrophobic nanoparticles at different particle concentrations c. For c = 0 we find a first-order liquid-liquid phase transition (LLPT). For c > 0 our simulations are consistent with a LLPT line ending in two critical points at low and high pressure P . For c = 25% at high P and low temperature T we find a dramatic decrease of compressibility K T , thermal expansion coefficient α P , and specific heat C P . Surprisingly, the effect is present also for c as low as 2.4%. We conclude that even a small presence of nanoscopic hydrophobes can drastically suppress therodynamic fluctuations, making the detection of the LLPT more difficult.

New experiments on water at the surface of proteins at very low temperature display intriguing dynamic behaviors. The extreme conditions of these experiments make it difficult to explore the wide range of thermodynamic state points needed to offer a suitable interpretation. Detailed simulations suffer from the same problem, where equilibration times at low temperature become extremely long. We show how Monte Carlo simulations and mean field calculations using a tractable model of water help interpret the experimental results. Here we summarize the results for bulk water and investigate the thermodynamic and dynamic properties of supercooled water at an interface.