Gustavo A. Appignanesi

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.

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.

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.

Structural and dynamical aspects of water in contact with a hydrophobic surface

Abstract.By means of molecular dynamics simulations we study the structure and dynamics of water molecules in contact with a model hydrophobic surface: a planar graphene-like layer. The analysis of the distributions of a local structural index indicates that the water molecules proximal to the graphene layer are considerably more structured than the rest and, thus, than the bulk. This structuring effect is lost in a few angstroms and is basically independent of temperature for a range studied comprising parts of both the normal liquid and supercooled states (240K to 320K). In turn, such structured water molecules present a dynamics that is slower than the bulk, as a consequence of their improved interactions with their first neighbors.

Influence of temperature, anions and size distribution on the zeta potential of DMPC, DPPC and DMPE lipid vesicles

The purpose of the work is to compare the influence of the multilamellarity, phase state, lipid head groups and ionic media on the origin of the surface potential of lipid membranes. With this aim, we present a new analysis of the zeta potential of multilamellar and unilamellar vesicles composed by phosphatidylcholines (PC) and phosphatidylethanolamines (PE) dispersed in water and ionic solutions of polarizable anions, at temperatures below and above the phase transition. In general, the adsorption of anions seems to explain the origin of the zeta potential in vesicles only above the transition temperature (Tc). In this case, the sign of the surface potential is ascribed to a partial orientation of head group moiety toward the aqueous phase. This is noticeable in PC head groups but not in PEs, due to the strong lateral interaction between PO and NH group in PE.

Experimental verification of rapid, sporadic particle motions by direct imaging of glassy colloidal systems.

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.

Behavior of water in contact with model hydrophobic cavities and tunnels and carbon nanotubes.

By means of molecular dynamics simulations we analyze the behavior of water in contact with model hydrophobic cavities and tunnels. We study the hydration and filling propensity of cavities and tunnels carved in alkane monolayers and, for comparison, we also study single-walled carbon nanotubes of similar size. Our results will determine the dependence of the filling propensity as a function of cavity size while revealing the dynamical nature of the process with alternation of filled and dry states. Concerning the tunnels built across the monolayer, we shall show that the minimum diameter in order to get filled is about twice as large as that for the carbon nanotubes, thus evidencing a more hydrophobic behavior. The existence of water-water hydrogen bonds, a necessary condition for penetration, will also be made evident.

Sub-nanoscale surface ruggedness provides a water-tight seal for exposed regions in soluble protein structure.

Soluble proteins must maintain backbone hydrogen bonds (BHBs) water-tight to ensure structural integrity. This protection is often achieved by burying the BHBs or wrapping them through intermolecular associations. On the other hand, water has low coordination resilience, with loss of hydrogen-bonding partnerships carrying significant thermodynamic cost. Thus, a core problem in structural biology is whether natural design actually exploits the water coordination stiffness to seal the backbone in regions that are exposed to the solvent. This work explores the molecular design features that make this type of seal operative, focusing on the side-chain arrangements that shield the protein backbone. We show that an efficient sealing is achieved by adapting the sub-nanoscale surface topography to the stringency of water coordination: an exposed BHB may be kept dry if the local concave curvature is small enough to impede formation of the coordination shell of a penetrating water molecule. Examination of an exhaustive database of uncomplexed proteins reveals that exposed BHBs invariably occur within such sub-nanoscale cavities in native folds, while this level of local ruggedness is absent in other regions. By contrast, BHB exposure in misfolded proteins occurs with larger local curvature promoting backbone hydration and consequently, structure disruption. These findings unravel physical constraints fitting a spatially dependent least-action for water coordination, introduce a molecular design concept, and herald the advent of water-tight peptide-based materials with sufficient backbone exposure to remain flexible.

Hydrophilic behavior of graphene and graphene-based materials

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.

Wrapping mimicking in drug-like small molecules disruptive of protein–protein interfaces

The discovery of small‐molecule drugs aimed at disrupting protein–protein associations is expected to lead to promising therapeutic strategies. The small molecule binds to the target protein thus replacing its natural protein partner. Noteworthy, structural analysis of complexes between successful disruptive small molecules and their target proteins has suggested the possibility that such ligands might somehow mimic the binding behavior of the protein they replace. In these cases, the molecules show a spatial and “chemical” (i.e., hydrophobicity) similarity with the residues of the partner protein involved in the protein–protein complex interface. However, other disruptive small molecules do not seem to show such spatial and chemical correspondence with the replaced protein. In turn, recent progress in the understanding of protein–protein interactions and binding hot spots has revealed the main role of intermolecular wrapping interactions: three‐body cooperative correlations in which nonpolar groups in the partner protein promote dehydration of a two‐body electrostatic interaction of the other protein. Hence, in the present work, we study some successful complexes between already discovered small disruptive drug‐like molecules and their target proteins already reported in the literature and we compare them with the complexes between such proteins and their natural protein partners. Our results show that the small molecules do in fact mimic to a great extent the wrapping behavior of the protein they replace. Thus, by revealing the replacement the small molecule performs of relevant wrapping interactions, we convey precise physical meaning to the mimicking concept, a knowledge that might be exploited in future drug‐design endeavors. Proteins 2012.