Detection of molecular behavior that characterizes systems using a deep learning approach.

Molecular dynamics (MD) simulation is a powerful computational method to observe molecular behavior. Although the detection of molecular behavior that characterizes systems is an important task in the study of MD, it is typically difficult and depends on human expert knowledge. Therefore, we propose a novel analysis scheme for MD data using deep neural networks. A key aspect of our scheme is the estimation of statistical distances between different ensembles that are probability distributions over the possible states of systems. This allows us to build low-dimensional embeddings of ensembles to visualize differences between systems in a compact metric space. Furthermore, the molecular behavior that contributes to the differences between systems can also be detected using the trained function of deep neural networks. The applicability of our scheme is demonstrated using three types of MD data. Our scheme could be a powerful tool to clarify the underlying physics in the molecular systems.

Molecular Dynamic Simulations to Probe Water Permeation Pathways of GPCRs.

Rhodopsin is a light-driven G protein-coupled receptor mediating signal transduction in eyes. The molecular dynamics (MD) simulations are powerful computational tools to investigate molecular behavior of proteins and internal water molecules which are related to the function of proteins; however, the MD simulations of the rhodopsin require several technical setups for accurate calculations. This chapter discusses practical methods for setting up the MD simulations of the rhodopsin [preparation of initial systems, condition files for MD simulation package GROMACS, and data analysis]. The data analysis includes the root mean square deviation (RMSD) and mapping of accessibility of water molecules.

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.

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

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.

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.

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.

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.