Via molecular dynamics simulations of the TIP4P/2005 water model, we study liquid water’s anomalous behavior at large negative pressure produced through isochoric cooling. We find that isochores without a pressure minimum can display “reentrant” behavior whereby a system that cavitates upon cooling can then rehomogenize upon further cooling. This behavior is a consequence of the underlying density maximum along the spinodal, but its actual manifestation in simulations is strongly influenced by finite size effects. These observations suggest that water under strong hydrophilic confinement may display richer phase behavior than hitherto assumed. This also suggests that propensity toward cavitation does not always correlate with greater tension, contrary to the prevailing assumption for interpreting water stretching experiments. We also show that a maximum spinodal density in water results in a locus of maximum compressibility and a minimum speed of sound that are independent from any influence of a liquid–liquid critical point (LLCP). However, we demonstrate that structural signatures of a Widom line, which likely emanates from an LLCP at elevated pressure, extend to large negative pressure, but such signatures are only observed upon sampling water’s underlying potential energy landscape, rather than the thermalized metastable liquid.

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.

Water freezes in a wide variety of low-temperature environments, from meteors and atmospheric clouds to soil and biological cells. In nature, ice usually nucleates at or near interfaces, because homogenous nucleation in the bulk can only be observed at deep supercoolings. Although the effect of proximal surfaces on freezing has been extensively studied, major gaps in understanding remain regarding freezing near vapor–liquid interfaces, with earlier experimental studies being mostly inconclusive. The question of how a vapor–liquid interface affects freezing in its vicinity is therefore still a major open question in ice physics. Here, we address this question computationally by using the forward-flux sampling algorithm to compute the nucleation rate in a freestanding nanofilm of supercooled water. We use the TIP4P/ice force field, one of the best existing molecular models of water, and observe that the nucleation rate in the film increases by seven orders of magnitude with respect to bulk at the same temperature. By analyzing the nucleation pathway, we conclude that freezing in the film initiates not at the surface, but within an interior region where the formation of double-diamond cages (DDCs) is favored in comparison with the bulk. This, in turn, facilitates freezing by favoring the formation of nuclei rich in cubic ice, which, as demonstrated by us earlier, are more likely to grow and overcome the nucleation barrier. The films considered here are ultrathin because their interior regions are not truly bulk-like, due to their subtle structural differences with the bulk.

The evaporation of water induced by confinement between hydrophobic surfaces has received much attention due to its suggested functional role in numerous biophysical phenomena and its importance as a general mechanism of hydrophobic self-assembly. Although much progress has been made in understanding the basic physics of hydrophobically induced evaporation, a comprehensive understanding of the substrate material features (e.g., geometry, chemistry, and mechanical properties) that promote or inhibit such transitions remains lacking. In particular, comparatively little research has explored the relationship between water’s phase behavior in hydrophobic confinement and the mechanical properties of the confining material. Here, we report the results of extensive molecular simulations characterizing the rates, free energy barriers, and mechanism of water evaporation when confined between model hydrophobic materials with tunable flexibility. A single-order-of-magnitude reduction in the material’s modulus results in up to a nine-orders-of-magnitude increase in the evaporation rate, with the corresponding characteristic time decreasing from tens of seconds to tens of nanoseconds. Such a modulus reduction results in a 24-orders-of-magnitude decrease in the reverse rate of condensation, with time scales increasing from nanoseconds to tens of millions of years. Free energy calculations provide the barriers to evaporation and confirm our previous theoretical predictions that making the material more flexible stabilizes the confined vapor with respect to liquid. The mechanism of evaporation involves surface bubbles growing/coalescing to form a subcritical gap-spanning tube, which then must grow to cross the barrier.

The functional native states of globular proteins become unstable at low temperatures, resulting in cold unfolding and impairment of normal biological function. Fundamental understanding of this phenomenon is essential to rationalizing the evolution of freeze-tolerant organisms and developing improved strategies for long-term preservation of biological materials. We present fully atomistic simulations of cold denaturation of an α-helical protein, the widely studied Trp-cage miniprotein. In contrast to the significant destabilization of the folded structure at high temperatures, Trp-cage cold denatures at 210 K into a compact, partially folded state; major elements of the secondary structure, including the α-helix, are conserved, but the salt bridge between aspartic acid and arginine is lost. The stability of Trp-cage’s α-helix at low temperatures suggests a possible evolutionary explanation for the prevalence of such structures in antifreeze peptides produced by cold-weather species, such as Arctic char. Although the 310-helix is observed at cold conditions, its position is shifted toward Trp-cage’s C-terminus. This shift is accompanied by intrusion of water into Trp-cage’s interior and the hydration of buried hydrophobic residues. However, our calculations also show that the dominant contribution to the favorable energetics of low-temperature unfolding of Trp-cage comes from the hydration of hydrophilic residues.

Ice formation is ubiquitous in nature, with important consequences in a variety of environments, including biological cells, soil, aircraft, transportation infrastructure, and atmospheric clouds. However, its intrinsic kinetics and microscopic mechanism are difficult to discern with current experiments. Molecular simulations of ice nucleation are also challenging, and direct rate calculations have only been performed for coarse-grained models of water. For molecular models, only indirect estimates have been obtained, e.g., by assuming the validity of classical nucleation theory. We use a path sampling approach to perform, to our knowledge, the first direct rate calculation of homogeneous nucleation of ice in a molecular model of water. We use TIP4P/Ice, the most accurate among existing molecular models for studying ice polymorphs. By using a novel topological approach to distinguish different polymorphs, we are able to identify a freezing mechanism that involves a competition between cubic and hexagonal ice in the early stages of nucleation. In this competition, the cubic polymorph takes over because the addition of new topological structural motifs consistent with cubic ice leads to the formation of more compact crystallites. This is not true for topological hexagonal motifs, which give rise to elongated crystallites that are not able to grow. This leads to transition states that are rich in cubic ice, and not the thermodynamically stable hexagonal polymorph. This mechanism provides a molecular explanation for the earlier experimental and computational observations of the preference for cubic ice in the literature.

We present the first simulation study of the impact of protein matrix structure on water sorption along with a new computational method to hydrate and dehydrate protein systems reversibly. To understand the impact of the underlying structure of the protein matrix on the hydration process, we compare three types of protein substrates comprised of Trp-cage miniproteins with varying degrees of monomer translational and orientational order and monomer denaturation. We show that the water sorption isotherms are qualitatively and quantitatively very similar for the Trp-cage matrices independently of the underlying degree of disorder, which is consistent with the experimental observation that the qualitative features of water sorption isotherms are nearly universal for globular proteins. We also show that the Trp-cage matrices with varying disorder share similar trends in volumetric swelling, solvent accessibility, and protein–water hydrogen bonding during the sorption processes, while hydrogen bonding between protein molecules depends sensitively on the matrix characteristics (crystal, powder, and thermally denatured powder). Volumetric swelling, solvent accessibility, and protein–water hydrogen bonds exhibit no hysteresis when plotted as a function of hydration level and are thus controlled exclusively by the protein’s water content.

We compare six lithium potentials by examining their ability to predict coexistence properties and liquid structure using molecular dynamics. All potentials are of the embedded-atom method type. The coexistence properties we focus on are the melting curve, vapor pressure, saturated liquid density, and vapor–liquid surface tension. For each property studied, the simulation results are compared to available experimental data in order to properly assess the accuracy of each potential. We find that the Cui second nearest-neighbor modified embedded-atom method potential is overall the most reliable potential, giving adequate agreement for most of the properties examined. For example, the zero-pressure melting point of this potential is shown to be around 443 K, while it is it known from experiments to be about 454 K. This potential also gives excellent agreement for the saturated liquid densities, even though no liquid properties were used in the fitting procedure. We conclude that even though this potential is the most reliable overall, there is still room for improvement in terms of obtaining more accurate agreement for some of the properties studied, specifically the slope of the melting pressure versus temperature.

Although hot, cold, and high pressure denaturation are well characterized, the possibility of negative pressure unfolding has received much less attention. Proteins under negative pressure, however, are important in applications such as medical ultrasound, and the survival of biopoloymers in the xylem and adjacent parenchyma cells of vascular plants. In addition, negative pressure unfolding is fundamentally important in obtaining a complete understanding of protein stability and naturally complements previous studies of high pressure denaturation. We use extensive replica-exchange molecular dynamics (REMD) simulations and thermodynamic analysis to obtain folding/unfolding equilibrium phase diagrams for the miniprotein trp-cage (α-structure, 20-residue), the GB1 β-hairpin (β-structure, 16-residue), and the AK16 peptide (α-helix, 16-residue). Although the trp-cage is destabilized by negative pressure, the GB1 β-hairpin and AK16 peptide are stabilized by this condition.

Permeation of water across the membrane/vapor and membrane/liquid-water interfaces of Nafion is studied using nonequilibrium molecular dynamics (NEMD) simulations, providing direct calculations of mass-transfer resistance. Water mass transfer within one nanometer of the vapor interface is shown to be 2 orders of magnitude slower than at any other point within the membrane, in qualitative agreement with permeation experiments. This interfacial resistance is much stronger than the resistance suggested by prior simulation work calculating self-diffusivity near the interface. The key difference between the prior approach and the NEMD approach is that the NEMD approach implicitly incorporates changes in solubility in the direction normal to the interface. Water is shown to be very insoluble near the vapor interface, which is rich in hydrophobic perfluorocarbon chains, in agreement with advancing contact angle experiments. Hydrophilic side chains are buried beneath this hydrophobic layer and aligned toward the interior of the membrane. Hydrophilic pores are not exposed to the vapor interface as proposed in prior theoretical work. At the membrane/liquid-water interface, highly swollen polymer chains extend into the liquid-water phase, forming a nanoscopically rough interface that is consistent with atomic force microscopy experiments. In these swollen conformations, hydrophilic side chains are exposed to the liquid-water phase, suggesting that the interface is hydrophilic, in agreement with receding contact angle experiments. The mass-transfer resistance of this interface is negligible compared to that of the bulk, in qualitative agreement with permeation experiments. The water activity at the vapor and liquid-water interfaces are nearly the same, yet large conformational and transport differences are observed, consistent with a mass-transfer-based understanding of Schroeder’s paradox for Nafion.

Of the numerous mechanisms that have been postulated to explain the origin of biological homochirality, asymmetric autocatalysis coupled with mutual inhibition is often cited as a plausible route to abiotic symmetry breaking. However, in a system closed to mass flow, the constraint of microscopic reversibility ensures that this far-from-equilibrium phenomenon can at best provide a temporary excursion from racemic equilibrium. Comparatively little attention has been paid in the literature to the manner in which such a closed system approaches equilibrium, examining the mechanisms and time scales involved in its transit. We use an elementary lattice model with molecular degrees of freedom, and satisfying microscopic reversibility, to investigate the temporal evolution of stochastic symmetry breaking in a closed system. Numerical investigation of the model’s behavior identified conditions under which the system’s evolution toward racemic equilibrium becomes extremely slow, allowing for long-time persistence of a symmetry-broken state. Strong mutual inhibition between enantiomers facilitates a “monomer purification” mechanism, in which molecules of the minor enantiomer are rapidly sequestered and a nearly homochiral state persists for long times, even in the presence of significant reverse reaction rates. Simple order of magnitude estimates show that with reasonable physical parameters a symmetry-broken state could persist over geologically relevant time scales.

We use umbrella sampling Monte Carlo and forward and reverse forward flux sampling (FFS) simulation techniques to compute the free energy barriers to evaporation of water confined between two hydrophobic surfaces separated by nanoscopic gaps, as a function of the gap width, at 1 bar and 298 K. The evaporation mechanism for small (1 × 1 nm2) surfaces is found to be fundamentally different from that for large (3 × 3 nm2) surfaces. In the latter case, the evaporation proceeds via the formation of a gap-spanning tubular cavity. The 1 × 1 nm2 surfaces, in contrast, are too small to accommodate a stable vapor cavity. Accordingly, the associated free energy barriers correspond to the formation of a critical-sized cavity for sufficiently large confining surfaces, and to complete emptying of the gap region for small confining surfaces. The free energy barriers to evaporation were found to be of O(20kT) for 14 Å gaps, and to increase by approximately ∼5kT with every 1 Å increase in the gap width. The entropy contribution to the free energy of evaporation was found to be independent of the gap width.

The drying of hydrophobic cavities is believed to play an important role in biophysical phenomena such as the folding of globular proteins, the opening and closing of ligand-gated ion channels, and ligand binding to hydrophobic pockets. We use forward flux sampling, a molecular simulation technique, to compute the rate of capillary evaporation of water confined between two hydrophobic surfaces separated by nanoscopic gaps, as a function of gap, surface size, and temperature. Over the range of conditions investigated (gaps between 9 and 14 Å and surface areas between 1 and 9 nm2), the free energy barrier to evaporation scales linearly with the gap between hydrophobic surfaces, suggesting that line tension makes the predominant contribution to the free energy barrier. The exponential dependence of the evaporation rate on the gap between confining surfaces causes a 10 order-of-magnitude decrease in the rate when the gap increases from 9 to 14 Å. The computed free energy barriers are of the order of 50kT and are predominantly enthalpic. Evaporation rates per unit area are found to be two orders of magnitude faster in confinement by the larger (9 nm2) than by the smaller (1 nm2) surfaces considered here, at otherwise identical conditions. We show that this rate enhancement is a consequence of the dependence of hydrophobic hydration on the size of solvated objects. For sufficiently large surfaces, the critical nucleus for the evaporation process is a gap-spanning vapor tube.

The first simulation study of water sorption on a flexible protein crystal is presented, along with a new computational approach for calculating sorption isotherms on compliant materials. The flexible ubiquitin crystal examined in the study exhibits appreciable sorption-induced swelling during fluid uptake, similar to that reported in experiments on protein powders. A completely rigid ubiquitin crystal is also examined to investigate the impact that this swelling behavior has on water sorption. The water isotherms for the flexible crystal exhibit Type II-like behavior with sorption hysteresis, which is consistent with experimental measurements on protein powders. Both of these behaviors, however, are absent in the rigid crystal, indicating that modeling flexibility is crucial for predicting water sorption behavior in protein systems. Changes in the enthalpy of adsorption, specific volume, and internal protein fluctuations that occur during sorption in the flexible crystal are also shown to compare favorably with experiment.Keywords: enthalpy of adsorption; molecular dynamics; Monte Carlo; protein crystal; water isotherm;

The reorientation dynamics of interfacial water molecules was recently shown to change non-monotonically next to surfaces of increasing hydrophilicity, with slower dynamics next to strongly hydrophobic (apolar) and very hydrophilic surfaces, and faster dynamics next to surfaces of intermediate hydrophilicities. Through a combination of molecular dynamics simulations and analytic modeling, we provide a molecular interpretation of this behavior. We show that this non-monotonic dependence arises from two competing effects induced by the increasing surface hydrophilicity: first a change in the hydration structure with an enhanced population of water OH bonds pointing toward the surface and second a strengthening of the water–surface interaction energy. The extended jump model, including the effects due to transition-state excluded volume and transition-state hydrogen-bond strength, provides a quasi-quantitative description of the non-monotonic changes in the water reorientation dynamics with surface hydrophilicity.

We present results from a molecular dynamics study of the dissociation behavior of carbon dioxide (CO2) hydrates. We explore the effects of hydrate occupancy and temperature on the rate of hydrate dissociation. We quantify the rate of dissociation by tracking CO2 release into the liquid water phase as well as the velocity of the hydrate−liquid water interface. Our results show that the rate of dissociation is dependent on the fractional occupancy of each cage type and cannot be described simply in terms of overall hydrate occupancy. Specifically, we find that hydrates with similar overall occupancy differ in their dissociation behavior depending on whether the small or large cages are empty. In addition, individual cages behave differently depending on their surrounding environment. For the same overall occupancy, filled small and large cages dissociate faster in the presence of empty large cages than when empty small cages are present. Therefore, hydrate dissociation is a collective phenomenon that cannot be described by focusing solely on individual cage behavior.

We present a molecular dynamics (MD) simulation study of the structure and energetics of thin films of water adsorbed on solid substrates at 240 K. By considering crystalline silica as a model hydrophilic surface, we systematically investigate the effect of film thickness on the hydrogen bonding, density, molecular orientation, and energy of adsorbed water films over a broad surface coverage range (δ). At the lowest coverage investigated (δ = 1 monolayer, ML), >90% of water molecules form three hydrogen bonds (H-bonds) with surface silanol groups and none with other water molecules; when δ = 1 ML, the most probable molecular orientation is characterized by both the molecular dipole and the OH vectors being parallel to the surface. As δ increases, water−water and water−surface interactions compete, leading to the appearance of an orientational structure near the solid−liquid interface characterized by the dipole moment pointing toward the silica surface. We find that the water−surface H-bond connectivity and energetics of the molecular layer nearest to the solid−liquid interface do not change as δ increases. Interfacial water molecules, therefore, are able to reorient and form water−water H-bonds without compromising water−surface interactions. The surface-induced modifications to the orientational structure of the adsorbed film propagate up to ∼1.4 nm from the solid−liquid interface when δ = 15.1 ML (a film that is ∼2.3 nm thick). For the thinner adsorbed films (δ ≤ 4.3 ML, thickness ≤0.8 nm) orientational correlations imposed by the solid−liquid and liquid−vapor interfaces are observed throughout.

Histogram-reweighting grand canonical Monte Carlo simulations were used to obtain the phase behavior of CO2–H2O mixtures over a broad temperature and pressure range (50 °C ≤ T ≤ 350 °C, 0 ≤ P ≤ 1000 bar). We performed a comprehensive test of several existing water (SPC, TIP4P, TIP4P2005, and exponential-6) and carbon dioxide (EPM2, TraPPE, and exponential-6) models using conventional Lorentz–Berthelot combining rules for the unlike-pair parameters. None of the models we studied reproduce adequately experimental data over the entire temperature and pressure range, but critical assessments were made on the range of T and P where particular model pairs perform better. Away from the critical region (T ≤ 250 °C), the exponential-6 model combination yields the best predictions for the CO2-rich phase, whereas the TraPPE/TIP4P2005 model combination provides the most accurate coexistence composition and pressure for the H2O-rich phase. Near the critical region (250 °C < T ≤ 350 °C), the critical points are not accurately estimated by any of the models studied, but the exponential-6 models are able to qualitatively capture the critical loci and the shape of the phase envelopes. Local improvements can be achieved at specific temperatures by introducing modification factors to the Lorentz–Berthelot combining rules, but the modified combining rule is still not able to achieve global improvements over the entire temperature and pressure range. Our work points to the challenge and importance of improving current atomistic models so as to accurately predict the phase behavior of this important binary mixture.

We employ the diffusion map approach as a nonlinear dimensionality reduction technique to extract a dynamically relevant, low-dimensional description of n-alkane chains in the ideal-gas phase and in aqueous solution. In the case of C₈ we find the dynamics to be governed by torsional motions. For C₁₆ and C₂₄ we extract three global order parameters with which we characterize the fundamental dynamics, and determine that the low free-energy pathway of globular collapse proceeds by a “kink and slide” mechanism, whereby a bend near the end of the linear chain migrates toward the middle to form a hairpin and, ultimately, a coiled helix. The low-dimensional representation is subtly perturbed in the solvated phase relative to the ideal gas, and its geometric structure is conserved between C₁₆ and C₂₄. The methodology is directly extensible to biomolecular self-assembly processes, such as protein folding.

We use infrared spectroscopy to study the evolution of protein folding intermediate structures on arbitrarily slow time scales by rapidly quenching thermally unfolded hen egg white lysozyme in a glassy matrix, followed by reheating of the protein to refold; upon comparison with differential scanning calorimetric experiments, low-temperature structural changes that precede the formation of energetic native contacts are revealed.

We present a molecular dynamics simulation study of the structure and dynamics of water confined between silica surfaces using β-cristobalite as a model template. We scale the surface Coulombic charges by means of a dimensionless number, k, ranging from 0 to 1, and thereby we can model systems ranging from hydrophobic apolar to hydrophilic, respectively. Both rotational and translational dynamics exhibit a nonmonotonic dependence on k characterized by a maximum in the in-plane diffusion coefficient, D||, at values between 0.6 and 0.8, and a minimum in the rotational relaxation time, τR, at k = 0.6. The slow dynamics observed in the proximity of the hydrophobic apolar surface are a consequence of β-cristobalite templating an ice-like water layer. The fully hydrophilic surfaces (k = 1.0), on the other hand, result in slow interfacial dynamics due to the presence of dense but disordered water that forms strong hydrogen bonds with surface silanol groups. Confinement also induces decoupling between translational and rotational dynamics, as evidenced by the fact that τR attains values similar to that of the bulk, while D|| is always lower than in the bulk. The decoupling is characterized by a more drastic reduction in the translational dynamics of water compared to rotational relaxation.

We use molecular dynamics simulations to study the influence of confinement on the dynamics of a nanoscopic water film at T = 300 K and ρ = 1.0 g cm−3. We consider two infinite hydrophilic (β-cristobalite) silica surfaces separated by distances between 0.6 and 5.0 nm. The width of the region characterized by surface-dominated slowing down of water rotational dynamics is ∼0.5 nm, while the corresponding width for translational dynamics is ∼1.0 nm. The different extent of perturbation undergone by the in-plane dynamic properties is evidence of rotational−translational decoupling. The local in-plane rotational relaxation time and translational diffusion coefficient collapse onto confinement-independent “master” profiles as long as the separation d ≥ 1.0 nm. Long-time tails in the perpendicular component of the dipole moment autocorrelation function are indicative of anisotropic behavior in the rotational relaxation.

We perform molecular dynamics simulations of water confined between atomically detailed hydrophobic, hydrophilic, and heterogeneous (patchy) nanoscale plates. We study the effects of temperature 220 ≤ T ≤ 300 K on confined water’s behavior at various pressures −0.2 ≤ P ≤ 0.2 GPa and plate separations 0.5 ≤ d ≤ 1.6 nm. Combining this with our earlier results on the same system [Giovambattista, N.; Rossky, P. J.; Debenedetti, P. G. Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys. 2006, 73, 041604; Giovambattista, N.; Rossky, P. J.; Debenedetti, P. G. J. Phys. Chem. C, 2007, 11, 1323], where pressure was varied at constant temperature, allows us to compare water’s behavior in nanoscale confinement, upon isobaric cooling and isothermal compression, corresponding to paths of interest in protein denaturation. At a fixed temperature, water confined between hydrophobic plates can form vapor, liquid, or crystal (bilayer ice) phases, depending on the values of P and d. The P−d phase diagrams at T = 300 K and T = 220 K show that cooling suppresses the vapor phase and stabilizes the liquid and crystal phases. The critical separation dc(P), below which vapor forms, shifts to lower values of d and P upon cooling. The density profiles show that, upon cooling, water approaches the hydrophobic plates. Hence, the effective hydrophobicity of the plate decreases as T decreases, consistent with the suppression of the vapor phase upon cooling. However, both the orientation of water’s molecules at the interface and the water contact angle on the hydrophobic surface show practically no temperature dependence. Simulations of water confined by heterogeneous plates decorated with hydrophobic and hydrophilic patches reveal that cooling leads to appreciable blurring of the differences between water densities at hydrophobic and hydrophilic surfaces. This observation, together with remarkable similarities in confined water’s response to isobaric cooling and to isothermal compression, suggests that the invasion of hydrophobic cavities by water is an important mechanism underlying both pressure and cold denaturation of proteins.

We formulate a two-dimensional lattice model to study the equilibrium phase behavior of a ternary mixture composed of two enantiomeric forms of a chiral molecule and a nonchiral liquid solvent. Numerical solution of the model invoking the mean-field approximation of statistical mechanics allows the calculation of a ternary phase diagram. A prominent feature of the phase diagram is the appearance of a mirror-image pair of triple points involving coexistence of a liquid phase enriched in one of the enantiomers with two solid phases: a racemic and an enantiopure crystal. Thus, over broad ranges of initial composition, including liquid mixtures containing almost equal amounts of the two enantiomers, the equilibrium state of the system produces liquid-phase chiral amplification. The calculations predict that chiral amplification is favored at low temperatures, and by strengthening those molecular interactions that stabilize the racemic crystal. The phase behavior that we obtain is qualitatively identical to that reported in a recent experimental study of solutions of amino acids, aimed at probing the liquid-phase control of asymmetric catalysis. Those results, and the present calculations that provide molecular-level insight into their underlying causes, suggest a possible thermodynamic scenario for the liquid-phase emergence of chiral imbalance in a prebiotic and presumably nearly racemic world.

To better understand the role of surface chemical heterogeneity in natural nanoscale hydration, we study via molecular dynamics simulation the structure and thermodynamics of water confined between two protein-like surfaces. Each surface is constructed to have interactions with water corresponding to those of the putative hydrophobic surface of a melittin dimer, but is flattened rather than having its native “cupped” configuration. Furthermore, peripheral charged groups are removed. Thus, the role of a rough surface topography is removed, and results can be productively compared with those previously observed for idealized, atomically smooth hydrophilic and hydrophobic flat surfaces. The results indicate that the protein surface is less hydrophobic than the idealized counterpart. The density and compressibility of water adjacent to a melittin dimer is intermediate between that observed adjacent to idealized hydrophobic or hydrophilic surfaces. We find that solvent evacuation of the hydrophobic gap (cavitation) between dimers is observed when the gap has closed to sterically permit a single water layer. This cavitation occurs at smaller pressures and separations than in the case of idealized hydrophobic flat surfaces. The vapor phase between the melittin dimers occupies a much smaller lateral region than in the case of the idealized surfaces; cavitation is localized in a narrow central region between the dimers, where an apolar amino acid is located. When that amino acid is replaced by a polar residue, cavitation is no longer observed.

Walter Kauzmann's classic 1948 review of liquid supercooling and glass formation drew attention to the temperatures at which (by extrapolation) enthalpies and entropies of liquid and crystal phases would appear to become equal. In the temperature–pressure (T, p) plane, the collection of such ‘Kauzmann temperatures’ generate characteristic curves. The present study examines the connection of those Kauzmann loci to equilibrium inverse melting phenomena, i.e. cases where isobaric heating causes freezing of the liquid. Such cases are associated with local minima or maxima in the melting curve pm(T), and we point out the possible relevance of melting curve maxima to the thermodynamics of protein folding. Both equal-enthalpy and equal-entropy Kauzmann curves must pass through melting curve extrema. Three thermodynamic identities have been obtained to describe the vicinity of these points; they involve, respectively, the slopes of the two Kauzmann curves, and the second temperature derivative of the melting pressure. The second of these three equations is formally identical to the first Ehrenfest relation for second-order phase transitions, but carries no phase-transition implication. For purposes of specific numerical illustration, the inverse-melting behavior displayed by 3He at low temperature has been analyzed in detail.

The size distribution of fine powders formed during the rapid expansion of supercritical solutions (RESS) depends on the operating conditions, as well as on the geometry of the expansion device. In order to meet product specifications and improve process control, a fundamental understanding of the interplay between nucleation, condensation, and coagulation during this type of expansion is needed. In this work, we model the particle dynamics resulting from homogeneous nucleation, condensation and coagulation during the subsonic expansion of a non-volatile solute in a supercritical fluid inside a cylindrical capillary. The calculations show that subsonic RESS is a very effective technique for producing particles in the 10–50 nm diameter range. The particle formation process is characterized by delayed nucleation, low particle number concentrations, precipitation of a comparatively small fraction of the total solute mass, and by a narrow size distribution. In a few cases where the expansion trajectory enters the fluid's vapor–liquid coexistence region, the particle formation exhibits early nucleation, strong coagulation, and higher particle number concentrations. In order to explain and describe quantitatively the much larger particle diameters found in actual RESS experiments, additional condensation and coagulation processes that occur in the transonic flow field outside the expansion device, and their interaction with this complex flow field, would also need to be incorporated.

In contrast to crystalline solids—for which a precise framework exists for describing structure1—quantifying structural order in liquids and glasses has proved more difficult because even though such systems possess short-range order, they lack long-range crystalline order. Some progress has been made using model systems of hard spheres2, 3, but it remains difficult to describe accurately liquids such as water, where directional attractions (hydrogen bonds) combine with short-range repulsions to determine the relative orientation of neighbouring molecules as well as their instantaneous separation. This difficulty is particularly relevant when discussing the anomalous kinetic and thermodynamic properties of water, which have long been interpreted qualitatively in terms of underlying structural causes. Here we attempt to gain a quantitative understanding of these structure–property relationships through the study of translational2, 3 and orientational4 order in a model5 of water. Using molecular dynamics simulations, we identify a structurally anomalous region—bounded by loci of maximum orientational order (at low densities) and minimum translational order (at high densities)—in which order decreases on compression, and where orientational and translational order are strongly coupled. This region encloses the entire range of temperatures and densities for which the anomalous diffusivity6, 7, 8, 9 and thermal expansion coefficient10 of water are observed, and enables us to quantify the degree of structural order needed for these anomalies to occur. We also find that these structural, kinetic and thermodynamic anomalies constitute a cascade: they occur consecutively as the degree of order is increased.

We use infrared spectroscopy to study the evolution of protein folding intermediate structures on arbitrarily slow time scales by rapidly quenching thermally unfolded hen egg white lysozyme in a glassy matrix, followed by reheating of the protein to refold; upon comparison with differential scanning calorimetric experiments, low-temperature structural changes that precede the formation of energetic native contacts are revealed.

The reorientation dynamics of interfacial water molecules was recently shown to change non-monotonically next to surfaces of increasing hydrophilicity, with slower dynamics next to strongly hydrophobic (apolar) and very hydrophilic surfaces, and faster dynamics next to surfaces of intermediate hydrophilicities. Through a combination of molecular dynamics simulations and analytic modeling, we provide a molecular interpretation of this behavior. We show that this non-monotonic dependence arises from two competing effects induced by the increasing surface hydrophilicity: first a change in the hydration structure with an enhanced population of water OH bonds pointing toward the surface and second a strengthening of the water–surface interaction energy. The extended jump model, including the effects due to transition-state excluded volume and transition-state hydrogen-bond strength, provides a quasi-quantitative description of the non-monotonic changes in the water reorientation dynamics with surface hydrophilicity.