Katsufumi Tomobe

Water Confined in the Local Field of Ions

Interionic distances are shorter in concentrated ionic solutions, thus instigating the interaction and overlap of hydration shells, as ions become separated by only one or two layers of water molecules. The simultaneous interaction of water with two oppositely charged ions has, so far, only been investigated by computer simulation studies, because the isolated vibrational spectroscopic signature of these molecules remains undetected. Our combined near-infrared spectroscopic and molecular dynamics simulation studies of alkali halide solutions present a distinct spectral feature, which is highly responsive to depletion of bulk water and merging of hydration shells. The analysis of this spectral feature demonstrates that absorption trends are in good agreement with the law of matching affinities, thus providing the first successful vibrational spectroscopic treatment of this topic. Combined with commonly observed near-infrared bands, this feature provides a spectral pattern that describes some relevant aspects of ionic hydration.

Effects of temperature, concentration, and isomer on the hydration structure in monosaccharide solutions

Water-monosaccharide coupled interactions are essential for the function, stability, and dynamics of all glycans. Using molecular dynamics simulations, we investigated the effects of temperature, concentration, and monosaccharide isomer on the hydration structure and water dynamics in the hydration shell of monosaccharides in solution. We found that perturbations of the hydrogen-bond (H-bond) network in the first hydration shell around each monosaccharide molecule can be separated into two regions: one rich in water molecules with donor H-bonds (in the 2.4-2.8 Å region) and the other rich in water molecules with abundant acceptor H-bonds (in the 2.8-3.3 Å region). Moreover, we investigated the dependencies of clustering and conversion of the conformers of the monosaccharides on temperature and concentration. Increasing the concentration enhances monosaccharide clustering in all the monosaccharide solutions, while cluster formation does not depend on temperature. In the clusters, some water molecules in the hydration shell are replaced with monosaccharide oxygen atoms, which contributes to the shrinkage of the hydration shell with increasing monosaccharide concentration. The monosaccharides basically adopt one of two conformers, the stable chair or the unstable boat conformer. We revealed that the hydration structures of the boat and chair conformers were dramatically different. As the temperature increases, the content of the chair conformer decreases. Thus, the conversion of conformers strongly affects the hydration structure around the monosaccharide. These results are critical to understand the important roles of the hydration structure in glycan solutions.

Velocity auto-correlation function of ions and water molecules in different concentrations, anions and ion clusters

The characteristics of ion solvation are important for electrochemical and biophysical phenomena because all such phenomena occur under the presence of solvated ions. In this study, we performed an all-atom molecular dynamics simulation of aqueous NaCl ranging from 0.5 to 3.0 M, and aqueous NaF, NaBr and NaI in 2.0 M, to investigate the time-averaged velocity auto-correlation function (TAVAF) of ions and water molecules. By comparing the concentrations and ion pairs, we observed three behaviours: (i) in the case of NaCl, the velocity auto-correlation of Cl− becomes weaker as the concentration increases, whereas those of Na+ are not clearly different, (ii) the intensity of fluctuations of the TAVAF gradually decreases following the decrease in ionic radius and (iii) every TAVAF of water molecules in ionic solutions is clearly lower than that of bulk because of the cage effect. Furthermore, we observed that the first minimum of the TAVAF in the cluster is smaller than that of the isolated ions. These results indicate that the diffusion of ions and water molecules is affected by cage effect, and that the generation of ion cluster affects the diffusion of ions.

Detection of Anomalous Dynamics for a Single Water Molecule

Water dynamics is of predominant importance in life, and it plays a critical role in chemical and biological systems. Many studies have reported nonbulk and anomalous dynamics of water molecules; however, a general method to detect the anomalous dynamics is yet to be established. Here, we develop a detection approach for the anomalous dynamics of a water molecule. Using a time series of the dipole vector of a water molecule, our approach achieves single-molecule detection of the anomalous dynamics for all water molecules in the system. Moreover, our approach quantifies the anomalous dynamics of a water molecule, which enables users to compare between different systems. In addition to the applicability, our approach has computational efficiency because it never calculates interactions with any other molecules. Experiments on five different systems of molecular dynamics simulations illustrate that our approach successfully detects the change points of water-molecule dynamics. These results demonstrate that our approach is a useful tool and provides a better understanding of dynamics of water molecules.

Link Prediction for Isolated Nodes in Heterogeneous Network by Topic-Based Co-clustering

This paper presents a new probabilistic generative model (PGM) that predicts links for isolated nodes in a heterogeneous network using textual data. In conventional PGMs, a link between two nodes is predicted on the basis of the nodes’ other existing links. This method makes it difficult to predict links for isolated nodes, which happens when new items are recommended. In this study, we first naturally expand the relational topic model (RTM) to a heterogeneous network (Hetero-RTM). However, this simple extension degrades performance in a link prediction for existing nodes. We present a new model called the Grouped Hetero-RTM that has both latent topics and latent clusterings. Through intensive experiments that simulate real recommendation problems, the Grouped Hetero-RTM outperforms baseline methods at predicting links for isolated nodes. This model, furthermore, performs as effectively as the stochastic block model in the link prediction for existing nodes. We also find that the Grouped Hetero-RTM is effective for various textual data such as item reviews and movie descriptions.

Origin of the blueshift of water molecules at interfaces of hydrophilic cyclic compounds

Molecular mechanism of the blueshift of water molecules. Water molecules at interfaces of materials exhibit enigmatic properties. A variety of spectroscopic studies have observed a high-frequency motion in these water molecules, represented by a blueshift, at both hydrophobic and hydrophilic interfaces. However, the molecular mechanism behind this blueshift has remained unclear. Using Raman spectroscopy and ab initio molecular dynamics simulations, we reveal the molecular mechanism of the blueshift of water molecules around six monosaccharide isomers. In the first hydration shell, we found weak hydrogen-bonded water molecules that cannot have a stable tetrahedral water network. In the water molecules, the vibrational state of the OH bond oriented toward the bulk solvent strongly contributes to the observed blueshift. Our work suggests that the blueshift in various solutions originates from the vibrational motions of these observed water molecules.

Water permeation through the internal water pathway in activated GPCR rhodopsin

Rhodopsin is a light-driven G-protein-coupled receptor that mediates signal transduction in eyes. Internal water molecules mediate activation of the receptor in a rhodopsin cascade reaction and contribute to conformational stability of the receptor. However, it remains unclear how internal water molecules exchange between the bulk and protein inside, in particular through a putative solvent pore on the cytoplasmic. Using all-atom molecular dynamics simulations, we identified the solvent pore on cytoplasmic side in both the Meta II state and the Opsin. On the other hand, the solvent pore does not exist in the dark-adapted rhodopsin. We revealed two characteristic narrow regions located within the solvent pore in the Meta II state. The narrow regions distinguish bulk and the internal hydration sites, one of which is adjacent to the conserved structural motif “NPxxY”. Water molecules in the solvent pore diffuse by pushing or sometimes jumping a preceding water molecule due to the geometry of the solvent pore. These findings revealed a total water flux between the bulk and the protein inside in the Meta II state, and suggested that these pathways provide water molecules to the crucial sites of the activated rhodopsin.

Instability of buried hydration sites increases protein subdomains fluctuations in the human prion protein by the pathogenic mutation T188R

The conformational change from the cellular prion protein (PrPc) to scrapie prion protein (PrPsc) is a key process in prion diseases. The prion protein has buried water molecules which significantly contribute to the stability of the protein; however, there has been no report investigating the influence on the buried hydration sites by a pathogenic mutation not adjacent to the buried hydration sites. Here, we perform molecular dynamics simulations of wild type (WT) PrPc and pathogenic point mutant T188R to investigate conformational changes and the buried hydration sites. In WT-PrPc, four buried hydration sites are identified by residence time and rotational relaxation analysis. However, there are no stable buried hydration sites in one of T188R simulations, which indicates that T188R sometimes makes the buried hydration sites fragile. We also find that fluctuations of subdomains S1-H1-S2 and H1-H2 increase in T188R when the buried hydration sites become unstable. Since the side chain of arginine which is replaced from threonine in T188R is larger than of threonine, the side chain cannot be embedded in the protein, which is one of the causes of the instability of subdomains. These results show correlations between the buried hydration sites and the mutation which is far from them, and provide a possible explanation for the instability by mutation.