Hydration and Nanoconfined Water: Insights from Computer Simulations.

The comprehension of the structure and behavior of water at interfaces and under nanoconfinement represents an issue of major concern in several central research areas like hydration, reaction dynamics and biology. From one side, water is known to play a dominant role in the structuring, the dynamics and the functionality of biological molecules, governing main processes like protein folding, protein binding and biological function. In turn, the same principles that rule biological organization at the molecular level are also operative for materials science processes that take place within a water environment, being responsible for the self-assembly of molecular structures to create synthetic supramolecular nanometrically-sized materials. Thus, the understanding of the principles of water hydration, including the development of a theory of hydrophobicity at the nanoscale, is imperative both from a fundamental and an applied standpoint. In this work we present some molecular dynamics studies of the structure and dynamics of water at different interfaces or confinement conditions, ranging from simple model hydrophobic interfaces with different geometrical constraints (in order to single out curvature effects), to self-assembled monolayers, proteins and phospholipid membranes. The tendency of the water molecules to sacrifice the lowest hydrogen bond (HB) coordination as possible at extended interfaces is revealed. This fact makes the first hydration layers to be highly oriented, in some situations even resembling the structure of hexagonal ice. A similar trend to maximize the number of HBs is shown to hold in cavity filling, with small subnanometric hydrophobic cavities remaining empty while larger cavities display an alternation of filled and dry states with a significant inner HB network. We also study interfaces with complex chemical and geometrical nature in order to determine how different conditions affect the local hydration properties. Thus, we show some results for protein hydration and, particularly, some preliminary studies on membrane hydration. Finally, calculations of a local hydrophobicity measure of relevance for binding and self-assembly are also presented. We then conclude with a few words of further emphasis on the relevance of this kind of knowledge to biology and to the design of new materials by highlighting the context-dependent and non-additive nature of different non-covalent interactions in an aqueous nanoenvironment, an issue that is usually greatly overlooked.

Relaxation pathway confinement in glassy dynamics.

We compute for an archetypical glass-forming system the excess of particle mobility distributions over the corresponding distribution of dynamic propensity, a quantity that measures the tendency of the particles to be mobile and reflects the local structural constraints. This enables us to demonstrate that, on supercooling, the dynamical trajectory in search for a relaxation event must deal with an increasing confinement of relaxation pathways. This "entropic funnel" of relaxation pathways built upon a restricted set of mobile particles is also made evident from the decay and further collapse of the associated Shannon entropy.

A unifying motif of intermolecular cooperativity in protein associations.

At the molecular level, most biological processes entail protein associations which in turn rely on a small fraction of interfacial residues called hot spots. Our theoretical analysis shows that hot spots share a unifying molecular attribute: they provide a third-body contribution to intermolecular cooperativity. Such motif, based on the wrapping of interfacial electrostatic interactions, is essential to maintain the integrity of the interface. Thus, our main result is to unravel the molecular nature of the protein association problem by revealing its underlying physics and thus by casting it in simple physical grounds. Such knowledge could then be exploited in rational drug design since the regions here indicated may serve as blueprints to engineer small molecules disruptive of protein-protein interfaces.

Temperature dependence of the structure of protein hydration water and the liquid-liquid transition.

We study the temperature dependence of the structure and orientation of the first hydration layers of the protein lysozyme and compare it with the situation for a model homogeneous hydrophobic surface, a graphene sheet. We show that in both cases these layers are significantly better structured than bulk water. The geometrical constraint of the interface makes the water molecules adjacent to the surface lose one water-water hydrogen bond and expel the fourth neighbors away from the surface, lowering local density. We show that a decrease in temperature improves the ordering of the hydration water molecules, preserving such a geometrical effect. For the case of graphene, this favors an ice Ih-like local structuring, similar to the water-air interface but in the opposite way along the c axis of the basal plane (while the vicinal water molecules of the air interface orient a hydrogen atom toward the surface, the oxygens of the water molecules close to the graphene plane orient a lone pair in such a direction). In turn, the case of the first hydration layers of the lysozyme molecule is shown to be more complicated, but still displaying signs of both kinds of behavior, together with a tendency of the proximal water molecules to hydrogen bond to the protein both as donors and as acceptors. Additionally, we make evident the existence of signatures of a liquid-liquid transition (Widom line crossing) in different structural parameters at the temperature corresponding to the dynamic transition incorrectly referred to as "the protein glass transition."

Quantitative investigation of the two-state picture for water in the normal liquid and the supercooled regime.

Several evidences have helped to establish the two-state nature of liquid water. Thus, within the normal liquid and supercooled regimes water has been shown to consist of a mixture of well-structured, low-density molecules and unstructured, high-density ones. However, quantitative analyses have faced the burden of unambiguously determining both the presence and the fraction of each kind of water "species". A recent approach by combining a local structure index with potential-energy minimisations allows us to overcome this difficulty. Thus, in this work we extend such study and employ it to quantitatively determine the fraction of structured molecules as a function of temperature for different densities. This enables us to validate predictions of two-state models.

Evidence of a two-state picture for supercooled water and its connections with glassy dynamics.

The picture of liquid water as consisting of a mixture of molecules of two different structural states (structured, low-density molecules and unstructured, high-density ones) represents a belief that has been around for long time awaiting for a conclusive validation. While in the last years some indicators have indeed provided certain evidence for the existence of structurally different "species", a more definite bimodality in the distribution function of a sound structural quantity would be desired. In this context, our present work combines the use of a structural parameter with a minimization technique to yield neat bimodal distributions in a temperature range within the supercooled liquid regime, thus clearly revealing the presence of two populations of differently structured water molecules. Furthermore, we elucidate the role of the inter-conversion between the identified two kinds of states for the dynamics of structural relaxation, thus linking structural information to dynamics, a long-standing issue in glassy physics.

Time evolution of dynamic propensity in a model glass former: the interplay between structure and dynamics.

By means of the isoconfigurational method, we calculate the change in the propensity for motion that the structure of a glass-forming system experiences during its relaxation dynamics. The relaxation of such a system has been demonstrated to evolve by means of rapid crossings between metabasins of its potential energy surface (a metabasin being a group of mutually similar, closely related structures which differ markedly from other metabasins), as collectively relaxing units (d-clusters) take place. We now show that the spatial distribution of propensity in the system does not change significantly until one of these d-clusters takes place. However, the occurrence of a d-cluster clearly decorrelates the propensity of the particles, thus ending up with the dynamical influence of the structural features proper of the local metabasin. We also show an important match between particles that participate in d-clusters and that which show high changes in their propensity.

Space and time dynamical heterogeneity in glassy relaxation. The role of democratic clusters.

In this work we review recent computational advances in the understanding of the relaxation dynamics of supercooled glass-forming liquids. In such a supercooled regime these systems experience a striking dynamical slowing down which can be rationalized in terms of the picture of dynamical heterogeneities, wherein the dynamics can vary by orders of magnitude from one region of the sample to another and where the sizes and timescales of such slowly relaxing regions are expected to increase considerably as the temperature is decreased. We shall focus on the relaxation events at a microscopic level and describe the finding of the collective motions of particles responsible for the dynamical heterogeneities. In so doing, we shall demonstrate that the dynamics in different regions of the system is not only heterogeneous in space but also in time. In particular, we shall be interested in the events relevant to the long-time structural relaxation or α relaxation. In this regard, we shall focus on the discovery of cooperatively relaxing units involving the collective motion of relatively compact clusters of particles, called 'democratic clusters' or d-clusters. These events have been shown to trigger transitions between metabasins of the potential energy landscape (collections of similar configurations or structures) and to consist of the main steps in the α relaxation. Such events emerge in systems quite different in nature such as simple model glass formers and supercooled amorphous water. Additionally, another relevant issue in this context consists in the determination of a link between structure and dynamics. In this context, we describe the relationship between the d-cluster events and the constraints that the local structure poses on the relaxation dynamics, thus revealing their role in reformulating structural constraints.

Do short-time fluctuations predict the long-time dynamic heterogeneity in a supercooled liquid?

Recent investigations have demonstrated that the short-time fluctuations in a supercooled liquid can be used as predictors of the long-time dynamic propensity (that is, the regions of the sample with enhanced tendency to be mobile within time scales on the order of the alpha -relaxation time). This could mean that the long-time dynamics (the actual mobility of the particles at such long times) would be implicit in the short-time dynamics or else, that the long-time dynamic propensity [as defined in A. Widmer-Cooper and P. Harrowell, Phys. Rev. Lett. 96, 185701 (2006)], while providing a measure of the degree of jamming of the local structure, would only be sensitive to the short time behavior. The first scenario is in clear disagreement with our recent finding that the influence of the local structure on dynamics (as determined by the propensity for motion) is only local in time, fading out at times close to the metabasin lifetime, much before the alpha -relaxation time. Thus, in this work we show that the short-time fluctuations in supercooled liquids do in fact represent precursors to the dynamics at intermediate times commensurate with the metabasin lifetime (being thus able to predict the regions of the sample that will present high propensity for motion at such stage) but that the dynamical behavior at later times of the alpha relaxation is unpredictable, in agreement with a metabasin random walk scenario.

Reproducibility of dynamical heterogeneities and metabasin dynamics in glass forming liquids: the influence of structure on dynamics.

The discovery that the propensity for particle motion in a supercooled liquid is completely determined by the initial structure pointed to the existence of a causal link between structure and dynamics in glassy systems. Here we demonstrate that this underlying influence of structure is only local in time, fading out beyond the metabasin lifetime much before the relaxation time. Thus, our results reveal the irreproducibility of metabasin dynamics and support the scenario of a random walk on metabasins for the long time diffusion.

Democratic particle motion for metabasin transitions in simple glass formers.

We use molecular dynamics computer simulations to investigate the local motion of the particles in a supercooled binary liquid. Using the concept of the distance matrix, we find that the alpha relaxation corresponds to a small number of crossings from one metabasin to a neighboring one. Each crossing is very rapid and involves the collective motion of O(40) particles that form a relatively compact cluster, whereas stringlike motions seem not to be relevant for these transitions. These compact clusters are thus potential candidates for the cooperatively rearranging regions proposed a long time ago by Adam and Gibbs.

Activated dynamics and timescale separation within the landscape paradigm: signature of complexity, diversity and glassiness.

The landscape paradigm has become a widespread picture within the realm of complex systems. Complex systems include a great variety of systems, ranging from glasses to biopolymers, which display a common dynamical behavior. Within this framework, the dynamics of a such a system can be envisioned as the search it performs on its (potential energy) landscape. This approach rests on the belief that the relaxation behavior depends only on generic features, irrespective of specific details and lies on the validity of a timescale separation scenario computationally corroborated but not properly validated yet form first principles. In this work we shall show that the prevalence of activated dynamics over other kinds of mechanisms determines the emergence of complex dynamical behavior. Thus, complexity and diversity are not intrinsic properties of a system but depend on the kind of exploration of the landscape. We shall focus mainly on an ample generic context (complex hierarchical systems which have been used as models of glasses, spin glasses and biopolymers) and a specific one (model glass formers). For the last case we shall be able to reveal (in mechanistic terms) the microscopic rationale for the occurrence of timescale separation. Furthermore, we shall explore the connections between these two up to now mostly unrelated contexts and the relation to a variational principle, and we shall reveal the conditions for the applicability of the landscape approach.