Structure of ice crystallized from supercooled water.

The freezing of water to ice is fundamentally important to fields as diverse as cloud formation to cryopreservation. At ambient conditions, ice is considered to exist in two crystalline forms: stable hexagonal ice and metastable cubic ice. Using X-ray diffraction data and Monte Carlo simulations, we show that ice that crystallizes homogeneously from supercooled water is neither of these phases. The resulting ice is disordered in one dimension and therefore possesses neither cubic nor hexagonal symmetry and is instead composed of randomly stacked layers of cubic and hexagonal sequences. We refer to this ice as stacking-disordered ice I. Stacking disorder and stacking faults have been reported earlier for metastable ice I, but only for ice crystallizing in mesopores and in samples recrystallized from high-pressure ice phases rather than in water droplets. Review of the literature reveals that almost all ice that has been identified as cubic ice in previous diffraction studies and generated in a variety of ways was most likely stacking-disordered ice I with varying degrees of stacking disorder. These findings highlight the need to reevaluate the physical and thermodynamic properties of this metastable ice as a function of the nature and extent of stacking disorder using well-characterized samples.

Communication: Conformation state diagram of polypeptides: a chain length induced α-ß transition.

By using a generic coarse grained polypeptide model, we perform multicanonical molecular dynamics simulations for determining the equilibrium conformation state diagram of a single homopolypeptide chain as a function of the chain length and temperature. The state diagram highlights the thermal regimes of stability for various conformational patterns in polypeptides, including swollen, random and collapsed coils, globular structures, extended and bended α helices, and compact ß bundles. Remarkably, at low temperatures we observe a sharp transition from extended α helix to compact ß bundles as the chain length increases. This finding indicates that the chain length is one of the intrisic factors that can trigger α-ß transformations in a broad class of polypeptides.

Phase behavior in suspensions of highly charged colloids.

Attractive interactions between like-charged aggregates (macromolecules, colloidal particles, or micelles) in solution due to electrostatic correlation effects are revisited. The associated phenomenon of phase separation in a colloidal solution of highly charged particles is directly observed in Monte Carlo simulations. We start with a simple, yet instructive, description of polarization effects in a "cloud" of counterions around a single charged aggregate and show how the ion-ion correlations can be mapped onto a classical analogue of the quantum-mechanical dispersion force. We then extend our treatment to the effective pair interaction between two such aggregates and provide an analysis of different interaction regimes, based on a simple coupling parameter. By computing the potential of mean force, we illustrate the physics behind the crossover between the regimes of pure repulsion and attraction with increasing counterion valency. Finally, we turn to semi grand NpT simulations of the corresponding bulk systems where mono- and multivalent ions can exchange with an external reservoir. Thus, the coagulation and phase separation phenomena, widely observed and used in real-life applications, are directly studied in these computer simulations.

Tracking polypeptide folds on the free energy surface: effects of the chain length and sequence.

Characterization of the folding transition in polypeptides and assessing the thermodynamic stability of their structured folds are of primary importance for approaching the problem of protein folding. We use molecular dynamics simulations for a coarse grained polypeptide model in order to (1) obtain the equilibrium conformation diagram of homopolypeptides in a broad range of the chain lengths, N = 10, ..., 100, and temperatures, T (in a multicanonical ensemble), and (2) determine free energy profiles (FEPs) projected onto an optimal, so-called "natural", reaction coordinate that preserves the height of barriers and the diffusion coefficients on the underlying free energy hyper-surface. We then address the following fundamental questions. (i) How well does a kinetically determined free energy landscape of a single chain represent the polypeptide equilibrium (ensemble) behavior? In particular, under which conditions might the correspondence be lost, and what are the possible implications for the folding processes? (ii) How does the free energy landscape depend on the chain length (homopolypeptides) and the monomer interaction sequence (heteropolypeptides)? Our data reveal that at low T values equilibrium structures adopted by relatively short homopolypeptides (N < 60) are dominated by α-helical folds which correspond to the primary and secondary minima of the FEP. In contrast, longer homopolypeptides (N > 70), upon quasi-equilibrium cooling, fold preferentially in ß-bundles with small helical portions, while the FEPs exhibit no distinct global minima. Moreover, subject to the choice of the initial configuration, at sufficiently low T, essentially metastable structures can be found and prevail far from the true thermodynamic equilibrium. We also show that, by sequence-enabling the polypeptide model, it is possible to restrict the chain to a very specific part of the configuration space, which results in substantial simplification and smoothing of the free energy landscape as compared to the case of the corresponding homopolypeptide.

Protein aggregation: kinetics versus thermodynamics.

In this study, we address the questions of how important is the kinetics in protein aggregation, and what are the intrinsic properties of proteins that cause this behavior. On the basis of our recent quantitative calculation of the equilibrium phase diagram of natively folded α-helical and ß-sheet forming peptides, we perform molecular dynamics simulations to demonstrate how the aggregation mechanism and end product depend on the temperature, concentration, and starting point in the phase diagram. The results obtained show that there are severe differences between the thermodynamically predicted and the kinetically obtained aggregate structures. The observed differences help to rationalize the suggestion that monomeric proteins in their native functional structure can be metastable with respect to the amyloid state, and that the native fold is a special property that protects them from aggregation.

Ice Ih-Water Interfacial Free Energy of Simple Water Models with Full Electrostatic Interactions.

We employ the cleaving approach to calculate directly the ice Ih-water interfacial free energy for the simple models of water, TIP4P, TIP4P-Ew, and TIP5P-E, with full electrostatic interactions evaluated via the Ewald sums. The results are in good agreement with experimental values, but lower than previously obtained for TIP4P-Ew and TIP5P-E by indirect methods. We calculate the interfacial free energies for basal, prism, and {112̅0} interfaces and find that the anisotropy of the TIP5P-E model is different from that of the TIP4P models. The effect of including full electrostatic interactions is determined to be smaller than 10% compared to the water models with damped Coulomb interactions, which indicates that the value of the ice-water interfacial free energy is determined predominantly by the short-range packing interaction between water molecules. We also observe a strong linear correlation between the interfacial free energy and the melting temperature of different water models.