Microscopic Origin of Hysteresis in Water Sorption on Protein Matrices.

Despite the importance of water sorption isotherms for a fundamental understanding of protein-water interactions, the microscopic origin of hysteresis between the adsorption and desorption branches is not well understood. Using our recently developed simulation technique, we compute the water sorption isotherms of two proteins, lysozyme and Trp-cage, a miniprotein. We explicitly compare protein-water interactions in adsorption and desorption processes, by analyzing local hydration in terms of hydrogen bonding, water density, and solvent-accessible surface area. We find that significant differences in hydration behavior between adsorption and desorption manifest themselves at the individual amino acid level, in particular around polar or charged residues. We confirm this observation by demonstrating that Trp-cage's hysteresis can be significantly reduced by mutating charged residues to alanine, a neutral and nonpolar amino acid.

Two-structure thermodynamics for the TIP4P/2005 model of water covering supercooled and deeply stretched regions.

One of the most promising frameworks for understanding the anomalies of cold and supercooled water postulates the existence of two competing, interconvertible local structures. If the non-ideality in the Gibbs energy of mixing overcomes the ideal entropy of mixing of these two structures, a liquid-liquid phase transition, terminated at a liquid-liquid critical point, is predicted. Various versions of the "two-structure equation of state" (TSEOS) based on this concept have shown remarkable agreement with both experimental data for metastable, deeply supercooled water and simulations of molecular water models. However, existing TSEOSs were not designed to describe the negative pressure region and do not account for the stability limit of the liquid state with respect to the vapor. While experimental data on supercooled water at negative pressures may shed additional light on the source of the anomalies of water, such data are very limited. To fill this gap, we have analyzed simulation results for TIP4P/2005, one of the most accurate classical water models available. We have used recently published simulation data, and performed additional simulations, over a broad range of positive and negative pressures, from ambient temperature to deeply supercooled conditions. We show that, by explicitly incorporating the liquid-vapor spinodal into a TSEOS, we are able to match the simulation data for TIP4P/2005 with remarkable accuracy. In particular, this equation of state quantitatively reproduces the lines of extrema in density, isothermal compressibility, and isobaric heat capacity. Contrary to an explanation of the thermodynamic anomalies of water based on a "retracing spinodal," the liquid-vapor spinodal in the present TSEOS continues monotonically to lower pressures upon cooling, influencing but not giving rise to density extrema and other thermodynamic anomalies.