Structure Of Water Molecules Research Articles

A disappearing metastable hydrate form of L-citrulline: Variable conformations in polymorphs and hydrates

An unstable monohydrate crystalline form of l-citrulline was harvested during high throughput solid form screening and its crystal structure and hydrogen bonding patterns are elaborated. The crystal structures of the previously reported anhydrous polymorphs and dihydrate are analysed and compared their conformational flexibility. Periodic Density Functional Theory (DFT) approach was employed to unveil the relative stability of citrulline upon hydration and its microscopic interactions with water molecules. The relative binding energy suggests the order of stability as dihydrate > citrulline (anhydrous) > monohydrate. Metastable nature of the monohydrate is reasoned based on the presence of water molecules in the channel structure, less interactions with the citrulline molecules and lower crystal density compared to the other solid forms. Unlike the reported dihydrate form, monohydrate transformed to the anhydrous citrulline (Form II) on spontaneous dehydration at ambient conditions because of their similar conformational flexibility. First time, we report reproducible crystallization process of polymorphs, dihydrate and a novel metastable monohydrate of l-Citrulline.

The role of hydration effects in 5-fluorouridine binding to SOD1: insight from a new 3D-RISM-KH based protocol for including structural water in docking simulations.

Misfolded Cu/Zn superoxide dismutase enzyme (SOD1) shows prion-like propagation in neuronal cells leading to neurotoxic aggregates that are implicated in amyotrophic lateral sclerosis (ALS). Tryptophan-32 (W32) in SOD1 is part of a potential site for templated conversion of wild type SOD1. This W32 binding site is located on a convex, solvent exposed surface of the SOD1 suggesting that hydration effects can play an important role in ligand recognition and binding. A recent X-ray crystal structure has revealed that 5-Fluorouridine (5-FUrd) binds at the W32 binding site and can act as a pharmacophore scaffold for the development of anti-ALS drugs. In this study, a new protocol is developed to account for structural (non-displaceable) water molecules in docking simulations and successfully applied to predict the correct docked conformation binding modes of 5-FUrd at the W32 binding site. The docked configuration is within 0.58Å (RMSD) of the observed configuration. The docking protocol involved calculating a hydration structure around SOD1 using molecular theory of solvation (3D-RISM-KH, 3D-Reference Interaction Site Model-Kovalenko-Hirata) whereby, non-displaceable water molecules are identified for docking simulations. This protocol was also used to analyze the hydrated structure of the W32 binding site and to explain the role of solvation in ligand recognition and binding to SOD1. Structural water molecules mediate hydrogen bonds between 5-FUrd and the receptor, and create an environment favoring optimal placement of 5-FUrd in the W32 binding site.

Improving identification and validation of water molecules in protein crystal structures with molecular dynamics simulations

Improving identification and validation of water molecules in protein crystal structures with molecular dynamics simulations

White Matter Segmentation Algorithm for DTI Images Based on Super-Pixel Full Convolutional Network

Diffusion tensor imaging (DTI) is a new imaging method that can be used to non-invasively measure the diffusion coefficient of water molecules in biological tissue structures in recent years. Since the DTI data is a tensor space, its segmentation is different from ordinary MRI images. Based on the existing deep learning model, an improved image semantic segmentation method based on super-pixels and conditional random field is proposed. Firstly, this paper uses the existing feature extraction model based on deep learning to obtain rough semantic segmentation results, including high-level semantic information of the image but lacking details of the image. In addition, the super-pixel segmentation algorithm is implemented to obtain super-pixels that carries more low-level information. Secondly, due to the lack of image details in rough segmentation results, the segmentation of the edge of the image is inaccurate. In this paper, a boundary optimization algorithm is proposed to optimize the edge segmentation accuracy of the rough results. Finally, the use of super-pixels for local boundary optimization can improve the segmentation accuracy. Experiments results show that this segment is a practical and effective method.

Laboratory synthesis and spectroscopic studies of hydrated Al-sulfates relevant to Mars

Orbital remote sensing has recently identified alunite as one of the types of Al-sulfate on Mars. As other types of hydrated Al-sulfates may also exist abundantly in the soil and rocks on Mars, it is important to perform systematic experimental investigations of the spectral characterization of hydrous Al-sulfates to identify and determine their potential distribution on Mars. We successfully used the humidity buffer technique to synthesize five alunogen series of Al-sulfates, Al2(SO4)3·xH2O (x = 0, 4, 8, 12, 14) and AlH(SO4)2·4H2O, with different degrees of hydration. X-ray diffraction (XRD) was used to identify them from the PDF 2004 database, except for the specie with 12 structural water molecules; the quantity of structural water in the latter was confirmed by thermogravimetry and differential scanning calorimetry measurements after heating to >500 °C. Raman, mid-infrared (MIR), and visible and near-infrared (VNIR) spectra were acquired to evaluate vibrational spectroscopic properties related to crystal structure. The prominent ν1 modes of SO4 tetrahedra of six Al-sulfates from Raman and MIR spectra have obvious shifts to higher wavenumbers (from 993.4 to 1133.6 cm−1) with decrease in hydration states. With no absorption bands from 250 to 1000 nm, all absorption features of the VNIR spectra of alunogen series of Al-sulfates are derived from overtones and combinations of fundamental vibrational modes from OH/H2O and SO4 groups, generally showing a red shift toward longer wavelengths with increasing hydration states. The XRD, Raman, MIR, and VNIR spectroscopic data of these Al-sulfates can provide crucial data supporting their identification for future remote sensing and in situ detection on Mars.

PyRod: Tracing Water Molecules in Molecular Dynamics Simulations.

Ligands entering a protein binding pocket essentially compete with water molecules for binding to the protein. Hence, the location and thermodynamic properties of water molecules in protein structures have gained increased attention in the drug design community. Including corresponding data into 3D pharmacophore modeling is essential for efficient high throughput virtual screening. Here, we present PyRod, a free and open-source Python software that allows for visualization of pharmacophoric binding pocket characteristics, identification of hot spots for ligand binding, and subsequent generation of pharmacophore features for virtual screening. The implemented routines analyze the protein environment of water molecules in molecular dynamics (MD) simulations and can differentiate between hydrogen bonded waters as well as waters in a protein environment of hydrophobic, charged, or aromatic atom groups. The gathered information is further processed to generate dynamic molecular interaction fields (dMIFs) for visualization and pharmacophoric features for virtual screening. The described software was applied to 5 therapeutically relevant drug targets, and generated pharmacophores were evaluated using DUD-E benchmarking sets. The best performing pharmacophore was found for the HIV1 protease with an early enrichment factor of 54.6. PyRod adds a new perspective to structure-based screening campaigns by providing easy-to-interpret dMIFs and purely protein-based pharmacophores that are solely based on tracing water molecules in MD simulations. Since structural information about cocrystallized ligands is not needed, screening campaigns can be followed, for which less or no ligand information is available. PyRod is freely available at https://github.com/schallerdavid/pyrod .

High Consistency of Structure-Based Design and X-Ray Crystallography: Design, Synthesis, Kinetic Evaluation and Crystallographic Binding Mode Determination of Biphenyl-N-acyl-β-d-Glucopyranosylamines as Glycogen Phosphorylase Inhibitors.

Structure-based design and synthesis of two biphenyl-N-acyl-β-d-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico-derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

Aluminium copper pillared clay membrane: application for dyestuff filtration

Membrane production from Al-Cu pillared clay has been carried out. Al-Cu pillared clay was made by mixing Al-Cu pillared solution in clay suspension with Al3+ and Cu2+ molar ratio of 8: 2 while molar ratio of [OH−]/[Cu2++ Al3+] was 2.2. The clay suspension was dried at 60°C for 5 hours to remove water molecules in the clay structure and then calcined for 4 hours at 200°C, 300°C and 400°C with a heating rate of 1°C/minute. The pillared clay obtained was then characterized by XRD and GSA. Further, the pillared clay was moulded into a membrane to further test its performance for dye filtration. The X-Ray Diffraction (XRD) results showed that the natural clay had a basal spacing (d001) of 15.08 Å. While, the pillared clay had dooi of 17.34 Å, 16.05 Å, 16.37 Å and 15.62 Å for the heating temperature of 60°C, 200°C, 300°C and 400°C respectively. The diameter of the Al-Cu pillared clay (38 Å) was greater than that of the natural clay (34 Å). Meanwhile, the membrane surface area was 50.48 m2/g, which was almost the same with natural clay (52.45 m2/g). The methylene blue filtration process displayed the clear-colour filtration results in all concentrations. Meanwhile, the measurements using the UV-Vis spectrophotometer produced a colour rejection of up to 99.92% and this increased as the methylene blue concentration was augmented. Whilst, the water flux was up to 3.51 × 10−6 kg min−1 m−2 Pa−1 and decreased with the increasing of concentration.

Diverse GPCRs exhibit conserved water networks for stabilization and activation

G protein-coupled receptors (GPCRs) have evolved to recognize incredibly diverse extracellular ligands while sharing a common architecture and structurally conserved intracellular signaling partners. It remains unclear how binding of diverse ligands brings about GPCR activation, the common structural change that enables intracellular signaling. Here, we identify highly conserved networks of water-mediated interactions that play a central role in activation. Using atomic-level simulations of diverse GPCRs, we show that most of the water molecules in GPCR crystal structures are highly mobile. Several water molecules near the G protein-coupling interface, however, are stable. These water molecules form two kinds of polar networks that are conserved across diverse GPCRs: (i) a network that is maintained across the inactive and the active states and (ii) a network that rearranges upon activation. Comparative analysis of GPCR crystal structures independently confirms the striking conservation of water-mediated interaction networks. These conserved water-mediated interactions near the G protein-coupling region, along with diverse water-mediated interactions with extracellular ligands, have direct implications for structure-based drug design and GPCR engineering.

Atomic-Level Characterization of C-Type Inactivation for Voltage-Gated Potassium Channels Shaker and hERG

C-type inactivation is a time-dependent process observed in many K+ channels whereby prolonged activation by an external stimulus leads to a reduction in ionic conduction. While C-type inactivation has been suggested as a constriction of the selectivity filter in pH-activated bacterial potassium channel KcsA, the structural basis of the C-type inactivation in voltage-gated potassium channels remains a long-standing question. Our recent computational study on KcsA revealed that the full opening of the intracellular gate could trigger a spontaneous and rapid conductive-to-constricted transition of the selectivity filter through an allosteric coupling. Following this finding, we captured the first stable constricted (inactive) structure in the voltage-gated potassium channel Shaker by inducing further opening of the intracellular gate in molecular dynamics simulations. The computational model displays several unique features different from the known constricted X-ray structures of the KcsA channel, which is also confirmed by a new crystallographic data for a shaker-like KcsA mutant from our lab. The conductive-to-constricted transition of the selectivity filter in simulation also reveals the underlying molecular mechanism of several key hydrogen bonds working as timer for C-type inactivation. Meanwhile, an asymmetrical constricted-like conformation is identified in our extended MD simulations for another voltage-gated potassium channel hERG. The constricted hERG filter involves a considerable reorientation of phenylalanine at position 627 along the selectivity filter to dock into the binding pocket occupied by the inactivating water molecules in the constricted KcsA structure. All of these results support the notion that constriction of the filter allosterically controlled by intracellular gate is a general molecular basis of C-type inactivation in a variety of potassium channels, but with alternative structural factors stabilizing the constricted conformation.

Crystal structure, large distortion of the Zn tetrahedron, and statistical displacement of water molecules in skorpionite

The crystal structures of skorpionite from the Skorpion zinc deposit in Namibia [Ca3Zn2(PO4)2CO3(OH)2·H2O; monoclinic; a = 19.0715(8), b = 9.3321(3), c = 6.5338(3) Å, β = 92.6773(12)°; space group C2/c] and [a = 19.0570(14), b = 9.3346(5), c = 6.5322(4) Å, β = 92.752(2)°; space group Cc] are analyzed using single–crystal X–ray diffraction and refined to yield R values of 0.0253 and 0.0272 for 1576 and 2446 unique reflections with Fo > 4σ(Fo), respectively. Hydrogen atoms in the structure determined by the difference Fourier method. Although two space groups, C2/c and Cc, are possible, the Cc space group without center of symmetry is more likely the structure of skorpionite, which shows that skorpionite is a ferroelectric mineral. The disordered structure is induced in skorpionite by twinning and/or domain structures because of the relaxation of the natural polarization caused by the arrangement of polarized water molecules. The space group Cc model without the center of symmetry eliminates the need for statistical distribution. Bond valence sum calculations and hydrogen bond networks can be explained in detail by the model. In the complicated structure caused by the chemical composition, the local structure with a non–ideal coordination environment is observed near the Zn sites. Hydrogen atoms are continuously arranged with regular arrangements of water molecules in the tunnel structure.

Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptor.

Misoprostol is a life-saving drug in many developing countries for women at risk of post-partum hemorrhaging due to its affordability, stability, ease of administration and clinical efficacy. However, misoprostol lacks receptor and tissue selectivities and thus its use is accompanied by a number of serious side-effects. The development of pharmacological agents combining the advantages of misoprostol with improved selectivity is hindered by the absence of atomic details of misoprostol action in labor induction. Here, we present the 2.5 Å resolution crystal structure of misoprostol free-acid form bound to the myometrium labor-inducing prostaglandin E2 receptor 3 (EP3). The active-state structure reveals a completely enclosed binding pocket containing a structured water molecule that coordinates misoprostol ring structure. Modelling of selective agonists in EP3 structure reveals rationales for selectivity. These findings will provide the basis for the next generation of uterotonic drugs that will be suitable for administration in low resource settings.

Effects of different oxygen-containing anions on the structure of water clusters

ABSTRACTUsing Ni(Im)62+ (Im = imidazole) as the structural unit, the effects of oxygen-containing anions, such as SO42-, NO3− and CO32- on the structure of water clusters were studied. The crystal structures of three compounds [Ni(Im)6][SO4(H2O)11] (1), [Ni(Im)6][(NO3)Cl(H2O)4] (2), and [Ni(Im)6][CO3(H2O)5] (3) were obtained. Using Mercury-3.8 software to analyze the above three crystal structures, find different anion of water clusters had a significant effect on the supramolecular structure. At the same time, it also significantly influences the number of water molecules in the crystal structure.

Interaction of Water with the Gypsum (010) Surface: Structure and Dynamics from Nonlinear Vibrational Spectroscopy and Ab Initio Molecular Dynamics.

Water-mineral interfaces are important for several environmental, industrial, biological, and geological processes. Gypsum, CaSO4·2H2O, is a widespread mineral of high technological, medical, and environmental relevance, but little is known about its surface structure and its interaction with water. A molecular-level understanding of gypsum/water interface is given here by a combined experimental/theoretical study. We investigate the structure and dynamics of water adsorbed from vapor on the gypsum (010) single-crystal surface at room temperature, combining sum-frequency generation (SFG) vibrational spectroscopy experiments and ab initio molecular dynamics (AIMD) simulations. The SFG spectra of gypsum at low relative humidity (RH) show an anisotropic arrangement of structural water molecules and the presence of dangling OH groups. The AIMD simulations allow a detailed assignment of the SFG spectra and show that the cleaved (010) surface rearranges to have only 25% of the OH groups pointing away from the surface. At higher RHs, the first adsorbed water layer binds to these OH groups and forms an anisotropic arrangement, but with the amount of free OH groups significantly suppressed and without any significant diffusion. Upon adsorption of a second water layer, although the topmost layer of molecules is more disordered and dynamic than the previous one, its structure is still influenced by the gypsum surface underneath because it has a much reduced amount of free OH groups with respect to the free surface of water, and a slower surface diffusion with respect to bulk water. The theoretical results corroborate the experimental ones and provide an accurate atomic characterization of the surface structure.

Microscopic mechanism of the interaction between water and formic acid-sodium chloride aerosol

As the effect of aerosol on the atmosphere is related to its hygroscopic properties, it is desirable to know the microscopic mechanism for the interaction between water and the aerosol consisting of inorganic and organic ingredients. In this work, molecular dynamics method is employed to investigate the behavior of formic acid - water systems without or with sodium chloride (NaCl), which represent simplified typical atmospheric aerosols. It mainly focuses on the effects of temperature, humidity and NaCl concentration on the structure and the interfacial properties of the aerosol at different simulation times. The results show that when the simulation time is 2 ns, with the increase of temperature the binary aggregate containing 360 H2O displays the demixed structure 1 (water clusters adsorb on the acid aggregate), the mixed structure (water molecules dissolve part of the acid aggregate) and the demixed structure 2 (acid molecules uniformly wrap around the water core). The stability of formic acid particles increases with the increase of NaCl concentration. Hence, the ternary aggregate containing 20 NaCl presents three identical structures, while only the first two structures can be observed for the ternary aggregate with 40/80 NaCl. At the equilibrium state, all three structures can be found in each aggregate containing 360 H2O, while the difference in structure can only be observed at intermediate temperatures. Correspondingly, only the first two structures are evidenced for all aggregates containing 120 H2O at the time of 2 ns and the equilibrium state. Hydrogen atoms (H(CH)) of the formic acid at the surface of all aggregates point toward the gas phase. Moreover, the ratio of organic molecules to inorganic molecules at aerosol surface increases with the increase of temperature and the decrease of NaCl and water content. Finally, the hygroscopic properties of the studied aerosols are discussed.

Micellar Parameters of Aqueous Solutions of Tween 20 and 60 at Different Temperatures: Volumetric and Viscometric Study

Density, viscosity and speed of sound of aqueous solutions of nonionic surfactants such as polyoxyethylene (20) sorbitan monolaurate (Tween 20) and polyoxyethylene (20) sorbitan monostearate (Tween 60) at T = 293, 303 and 313 K are reported. From these measured values different parameters such as, for example, isentropic compressibility, molecular free length, acoustic impedance, primary hydration numbers and internal pressure have been calculated and employed to discuss molecular packing, structural alteration and molecular interactions. The variation in these parameters with temperature indicates that the mobility of surfactant molecules increases the disordered state of the liquid (surfactant + water) due to irregular packing of the molecules. Also, for Tween 20 solutions, more conversion to bulk water of the structured water molecules was observed, obtaining lower compressibilities and higher values of hydration numbers as well as internal pressure for a given T.

Improved rate performance of Prussian blue cathode materials for sodium ion batteries induced by ion-conductive solid-electrolyte interphase layer

Prussian blue (PB) and its analogues (PBAs) are promising cathode materials for sodium ion batteries (SIBs) because of their wide diffusion tunnels for sodium ions. However, water molecules typically contained within PB structures have been hypothesized to undermine their stability and rate performance. Here we report that zeolite water molecules in PB structures may induce the formation of Na2CO3 as one of the main components in SEI layer on the surface of PB materials. From PB samples containing zeolite water synthesized via a solvothermal method at different temperatures, a specific capacity of 113 mAh g−1 is demonstrated at 10 mA g−1, with a capacity retention of 75% at 1000 mA g−1. Cycling tests reveal a capacity loss of only 1.2% after 100 cycles at 200 mA g−1. It is suggested that Na2CO3 contained in the SEI layer not only protects the electrode materials from side reactions with the electrolyte, but also facilitates quick charge transfer at the interfaces, leading to improved electrochemical performances.

Placement of Water Molecules in Protein Structures: From Large-Scale Evaluations to Single-Case Examples.

Water molecules are of great importance for the correct representation of ligand binding interactions. Throughout the last years, water molecules and their integration into drug design strategies have received increasing attention. Nowadays a variety of tools are available to place and score water molecules. However, the most frequently applied software solutions require substantial computational resources. In addition, none of the existing methods has been rigorously evaluated on the basis of a large number of diverse protein complexes. Therefore, we present a novel method for placing water molecules, called WarPP, based on interaction geometries previously derived from protein crystal structures. Using a large, previously compiled, high-quality validation set of almost 1500 protein-ligand complexes containing almost 20 000 crystallographically observed water molecules in their active sites, we validated our placement strategy. We correctly placed 80% of the water molecules within 1.0 Å of a crystallographically observed one.

Dehydration Study of Piracetam Co-Crystal Hydrates

A hydrate of co-crystal of piracetam and 3,5-dihydroxybenzoic acid was obtained via crystallization from water. Single-crystal X-ray data show that piracetam/3,5-dihydroxybenzoic acid tetrahydrate (P35TH) crystallizes in the triclinic system with a P1 space group. The physicochemical properties of co-crystal hydrate were characterized using powder X-ray diffractometry, differential scanning calorimetry (DSC), thermogravimetric analyzer (TGA), and FTIR spectroscopy. The dehydration kinetics of P35TH was monitored at various temperatures and heating rates by DSC and TGA. Activation energy of P35TH dehydration was obtained using temperature ramp DSC, isothermal and nonisothermal TGA methods. Kinetic analysis of isothermal TGA data was fitted to various solid-state reaction models. Mechanistic models derived from isothermal dehydration kinetic data are best described as a 2-dimensional diffusion mechanism. A correlation was noted between the dehydration behavior and the bonding environment of the water molecules in the crystal structure. This study is a good demonstration of complexity of co-crystal hydrate and their dehydration behavior.

Temperature-induced hierarchical Tremella-like and Pinecone-like NiO microspheres for high-performance supercapacitor electrode materials

Nickel oxide (NiO) microspheres with tremella-like and pinecone-like structures were facilely synthesized using the solvothermal method, followed by calcination treatment. NiO structures were controlled by adjusting the calcination temperature of the as-prepared nitrate precursor. NiO microspheres and nitrate precursors were investigated using a number of techniques. Tremella-like NiO (TN4-C1) microspheres obtained at 350 °C show higher surface areas, thinner secondary nanosheets, larger cavities, and smaller crystal sizes than pinecone-like NiO (PN4-C2 and PN4-C3) microspheres obtained at 600 and 850 °C, respectively. Electrochemical performances of TN4-C1, PN4-C2, and PN4-C3 were investigated using cyclic voltammetry and galvanostatic charging/discharging techniques. At 3 A g−1, TN4-C1 exhibits a maximum specific capacitance of 3242 F g−1, which is significantly higher than that of PN4-C2 (891 F g−1) and PN4-C3 (486 F g−1) and is close to its theoretical specific capacitance. This finding can be attributed to the superior morphology of TN4-C1 and its abundant structural water molecules, which ensure rapid ion diffusion. This study provides a facile and feasible method of preparing porous transition-metal-oxide-based electrode materials with specific morphology and hierarchical structure.