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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Soluble proteins must protect their structural integrity from water attack by wrapping interactions which imply the clustering of nonpolar residues around the backbone hydrogen bonds. Thus, poorly wrapped hydrogen bonds constitute defects which have been identified as promoters of protein associations since they favor the removal of hydrating molecules. More specifically, a recent study of our group has shown that wrapping interactions allow the successful identification of protein binding hot spots. Additionally, we have also shown that drugs disruptive of protein-protein interfaces tend to mimic the wrapping behavior of the protein they replace. Within this context, in this work we study wrapping three body interactions related to the oncogenic Y220C mutation of the tumor suppressor protein p53. Our computational results rationalize the oncogenic nature of the Y220C mutation, explain the binding of a drug-like molecule already designed to restore the function of p53 and provide clues to help improve this function-rescue strategy and to apply in other drug design or re-engineering techniques. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We analyze data from confocal microscopy experiments of a colloidal suspension to validate predictions of rapid sporadic events responsible for structural relaxation in a glassy sample. The trajectories of several thousand colloidal particles are analyzed, confirming the existence of such rapid events responsible for the structural relaxation of significant regions of the sample, and complementing prior observations of dynamical heterogeneity. Thus, our results provide the first direct experimental verification of the emergence of relatively compact clusters of mobility which allow the dynamics to transition between the large periods of local confinement within its potential energy surface, in good agreement with the picture envisioned long ago by Adam and Gibbs and Goldstein. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Graphene and the graphene-based materials like graphite, carbon nanotubes, and fullerenes are not only usually regarded as hydrophobic but also have been widely employed as paradigms for the investigation of the behavior of water under nonpolar confinement, a question of major concern for fields ranging from biology to materials design. However, some experimental and theoretical insights seem to contradict, at least partially, such a picture. In this work, we will provide firm evidence for a neat hydrophilic nature of graphene surfaces. Our molecular dynamics studies will demonstrate that parallel graphene sheets present a strong tendency to remain fully hydrated for moderately long times (even when the equilibrium state is indeed the collapse of the plates), and thus, they are less prone to self-assembly than model hydrophobic surfaces we shall employ as control which readily undergo a hydrophobic collapse. Potential of mean force calculations will indeed make evident that the solvent exerts a repulsive contribution on the self-assembly of graphene surfaces. Moreover, we shall also quantify graphene hydrophilicity by means of the calculation of water density at two pressures and water density fluctuations. This latter study has never been performed on graphene and represents a means both to confirm and to quantify its neat hydrophilic behavior. We shall also make evident the relevance of the mildly attractive water-carbon interactions, since their artificial weakening will be shown to revert from typically hydrophilic to typically hydrophobic behavior. [ABSTRACT FROM AUTHOR]

We introduce a robust approach for characterizing spatially and temporally heterogeneous behavior within a system based on the evolution of dynamic fluctuations averaged over different space lengths and timescales. We apply it to investigate the dynamics in two canonical systems as the glass transition is approached: simulated Lennard-Jones liquids and experimental dense colloidal suspensions. In both cases the onset of glassiness is marked by spatially localized dynamic fluctuations originating in regions of correlated mobile particles. By removing the trivial system size dependence we show that the spatial heterogeneity of the dynamics extends to large length scales containing tens to hundreds of particles, corresponding to the timescale of maximally non-Gaussian dynamics. [ABSTRACT FROM AUTHOR]

Ligands must displace water molecules from their corresponding protein surface binding site during association. Thus, protein binding sites are expected to be surrounded by non-tightly-bound, easily removable water molecules. In turn, the existence of packing defects at protein binding sites has been also established. At such structural motifs, named dehydrons, the protein backbone is exposed to the solvent since the intramolecular interactions are incompletely wrapped by non-polar groups. Hence, dehydrons are sticky since they depend on additional intermolecular wrapping in order to properly protect the structure from water attack. Thus, a picture of protein binding is emerging wherein binding sites should be both dehydrons rich and surrounded by easily removable water. In this work we shall indeed confirm such a link between structure and dynamics by showing the existence of a firm correlation between the degree of underwrapping of the protein chain and the mobility of the corresponding hydration water molecules. In other words, we shall show that protein packing defects promote their local dehydration, thus producing a region of 'hot' interfacial water which might be easily removed by a ligand upon association. Graphical abstract: [ABSTRACT FROM AUTHOR]

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." [ABSTRACT FROM AUTHOR]