Experimental verification of democratic 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 rapid sporadic events responsible for the structural relaxation of significant regions of the sample, and complementing prior observations of dynamical heterogeneity. The emergence of relatively compact clusters of mobility allows 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.Comment: 4 pages, 5 figure

Metabasin dynamics and local structure in supercooled water

We employ the Distance Matrix method to investigate metabasin dynamics in supercooled water. We find that the motion of the system consists in the exploration of a finite region of configuration space (enclosing several distinct local minima), named metabasin, followed by a sharp crossing to a different metabasin. The characteristic time between metabasin transitions is comparable to the structural relaxation time, suggesting that these transitions are relevant for the long time dynamics. The crossing between metabasins is accompanied by very rapid diffusional jumps of several groups of dynamically correlated particles. These particles form relatively compact clusters and act as cooperative relaxing units responsible for the density relaxation. We find that these mobile particles are often characterized by an average coordination larger than four, i.e. are located in regions where the tetrahedral hydrogen bond network is distorted

A structural determinant of the behavior of water at hydration and nanoconfinement conditions

Liquid water is reluctant to lose hydrogen-bond coordination. Here we reveal that it also demands contraction and reorientation of the second molecular shell to compensate for coordination defects. Such molecular principle will be shown to lie at the heart of the two-liquids scenario and to determine the behavior of water in hydration and nanoconfinement. Furthermore, it allows to define conditions for wettability (quantifying hydrophobicity and predicting drying transitions), thus opening the possibility to elucidate the active role of water in central fields of research

Comparing the performance of two structural indicators for different water models while seeking for connections between structure and dynamics in the glassy regime

In this work, we compare the performance of two structural indicators based on the degree of translational order up to the second coordination shell in three water models: SPC/E, TIP4P/2005, and TIP5P. Beyond directly contrasting their distributions for different temperatures to evidence their usefulness in estimating the fraction of structured and unstructured molecules and, when possible, their classification capability, we also correlate them with an indirect measure of structural constraint: the dynamic propensity. Furthermore, this procedure enables us to show the existence of evident correlations between structural and dynamical information. More specifically, we find that locally structured molecules display a preference for low dynamic propensity values and, more conspicuously, that locally unstructured molecules are extremely subject to high dynamic propensity. This result is particularly relevant for the supercooled regime where the establishment of firm links between the structure and dynamics has remained rather elusive since the occurrence of dynamics that vary in orders of magnitude upon supercooling usually contrast with barely noticeable overall structural changes.Fil: Verde, Alejandro Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Montes de Oca, Joan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Accordino, Sebastián R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Alarcón, Laureano M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Appignanesi, Gustavo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin

Spatiotemporal intermittency and localized dynamic fluctuations upon approaching the glass transition

We introduce a new and robust approach for characterizing spatially and temporally heterogeneous behavior within a system based on the evolution of dynamic fuctuations once averaged over different space lengths and time scales. 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. We find that in both cases the onset of glassines is marked by spatially localized dynamic fluctuations originating in regions of correlated mobile particles. By removing the trivial system size dependence of the fluctuations we show that such regions contain tens to hundreds of particles for time scales corresponding to maximally non-Gaussian dynamics.Comment: New analysis technique introduced, and applied to previously published dat

Wrapping effects within a proposed function-rescue strategy for the Y220C oncogenic mutation of protein p53.

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

Hydrogen Bond Dynamic Propensity Studies for Protein Binding and Drug Design.

We study the dynamic propensity of the backbone hydrogen bonds of the protein MDM2 (the natural regulator of the tumor suppressor p53) in order to determine its binding properties. This approach is fostered by the observation that certain backbone hydrogen bonds at the p53-binding site exhibit a dynamical propensity in simulations that differs markedly form their state-value (that is, formed/not formed) in the PDB structure of the apo protein. To this end, we conduct a series of hydrogen bond propensity calculations in different contexts: 1) computational alanine-scanning studies of the MDM2-p53 interface; 2) the formation of the complex of MDM2 with the disruptive small molecule Nutlin-3a (dissecting the contribution of the different molecular fragments) and 3) the binding of a series of small molecules (drugs) with different affinities for MDM2. Thus, the relevance of the hydrogen bond propensity analysis for protein binding studies and as a useful tool to complement existing methods for drug design and optimization will be made evident

Distribution of the number of water molecules within the desolvation domain of the HB CYS 220 - THR 155.

<p>Pdbs 2VUK (T-p53C-Y220C-PhiKan083; μ = 8.743 and σ = 1.720) and 2J1X (T-p53C-Y220C; μ = 11.819 and σ = 2.111).</p

T-p53C-Y220C in complex with PhiKan083 (pdb: 2VUK).

<p>Dehydrons in the protein are depicted by green bars joining the two residues paired by the HB, while green thin lines are wrapping interactions with the small molecule.</p

Wrapping study of the T-p53C protein molecule (pdb: 1UOL), the T-p53C-Y220C protein (pdb: 2J1X) and the complex between p53C-Y220C and the small molecule PhiKan083 (pdb: 2VUK).

<p>The wrapping value of the HBs of the protein chain that occur at the mutation site (mutation Y220C) and that are targeted by PhiKan083 is indicated respectively as ρ_A-wt, ρ_A and ρ_AD.</p