Placing Water Molecules Research Articles

Insights into FinFET Structure Collapse: A Reactive Force Field-Based Molecular Dynamics Investigation

As miniaturization progresses, pattern collapse during the drying step of wet cleaning processes has become a critical issue in the semiconductor industry. In this study, we used reactive molecular dynamics simulations to analyze pattern collapse, with a focus on bondings and reactions. To simulate pattern deformation during the drying process of wet cleaning, we created a FinFET model as a HAR structure. The surface of this model was terminated with hydrogen atoms. The widths between the patterns were changed in order to create a Laplace pressure difference when water molecules were placed on the surface. The model was simulated by placing water molecules up to half the height of the pattern. As a result, the pattern was deformed. Furthermore, by removing water molecules and changing the Laplace pressure balance, it was found that the pattern contacted each other at the tip. The pattern remained in contact when water molecules were removed from the model. In the contact area, the covalent bonds, such as Si-Si and Si-O-Si, were not formed, but instead, hydrogen-to-hydrogen van der Waals bonds were formed between patterns. We calculated the total van der Waals forces between hydrogen atoms at the contact surfaces using the Hamaker equation and calculated the elastic force of the patterns using the beam deflection formula. Our calculations showed that the total van der Waals forces between hydrogen atoms at the contact surfaces were larger than the elastic force of the patterns, indicating that van der Waals forces could be a factor in maintaining the contact of the patterns.

Predicting Positions of Bridging Water Molecules in Nucleic Acid-Ligand Complexes.

Over the past two decades, interests in DNA and RNA as drug targets have been growing rapidly. Following the trends observed with protein drug targets, computational approaches for drug design have been developed for this new class of molecules. Our efforts toward the development of a universal docking program, Fitted, led us to focus on nucleic acids. Throughout the development of this docking program, efforts were directed toward displaceable water molecules which must be accurately located for optimal docking-based drug discovery. However, although there is a plethora of methods to place water molecules in and around protein structures, there is, to the best of our knowledge, no such fully automated method for nucleic acids, which are significantly more polar and solvated than proteins. We report herein a new method, Splash'Em (Solvation Potential Laid around Statistical Hydration on Entire Macromolecules) developed to place water molecules within the binding cavity of nucleic acids. This fast method was shown to have high agreement with water positions in crystal structures and will therefore provide essential information to medicinal chemists.

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.

Diffusion study for chloride ions and water molecules in C-S-H gel in nano-scale using molecular dynamics: Case study of tobermorite

Porous materials such as concrete could be subjected to aggressive ions transport. Durability of cement paste is extremely depended on water and ions penetration into its interior sections. These ions transport could lead different damages depending on reactivity of ions, their concentrations and diffusion coefficients. In this paper, chloride diffusion process in cement hydrates is simulated at atomistic scale using molecular dynamics. Most important phase of cement hydrates is calcium silicate hydrate (C-S-H). Tobermorite, one of the most famous crystal analogues of C-S-H, is used as substrate in the simulation model. To conduct simulation, a nanopore is considered in the middle of simulation cell to place water molecules and aggressive ions. Different chloride salts are considered in models to find out which one is better for calculation of the transport properties. Diffusion coefficients of water molecules and chloride ions are calculated and validated with existing analytical and experimental works. There are relatively good agreements among simulation outputs and experimental results.

Computational Study on Protolytic Dissociation of HCl and HF in Aqueous Solution

The protolytic dissociation process of hydrochloric acid (HCl) and hydrofluoric acid (HF) is studied using the B3LYP and MP2 methods with the 6-311+G(d,p) basis set in the gas phase and in aqueous solution. To study the phenomena in detail, discrete and discrete/continuum models were applied by placing water molecules in various positions around the acid. The dissociation process was studied using the thermodynamic cycle involving the structures optimized both in the gas phase and in aqueous solution and was analyzed with two key energy factors, relaxation free energy (ΔGRex(g)) and solvation free energy (ΔGs). Based on the results, we could understand the dissociation mechanism and wish to propose the best way to study acid dissociation process using the CPCM methodology in aqueous solution.

Interaction of caffeine dimers with water molecules

Stability of caffeine dimers in the presence of surrounding water molecules was investigated by performing ab initio calculations at B3LYP/CBSB7 level of theory. Dimers were constructed by placing geometry optimized monomers at different relative orientations. These dimers were then fully geometry optimized at the same level of theory. Dimer–water interaction was modeled in two ways. Dimers were geometry optimized in aqueous medium using polarizable conductor calculation model. The energy, enthalpy and Gibbs energy of dimer formation was then calculated. It was found that the thermodynamic parameters are much deviated from experimental values. Caffeine dimer water interactions were also modeled by placing water molecules around the dimer at locations where hydrogen bonds could form. In this manner, the number of water molecules was increased up to six. It was observed that the water molecules form hydrogen bonds with both the caffeine molecules. The caffeine–caffeine inter-plane distance increased from 3.6Å for isolated caffeine dimers (gas phase) up to 3.9Å for dimer water clusters. Formation energy change (ΔE) of caffeine dimers, depending on their relative orientation in gas phase, ranged from −5.2 to −6.0kcalmol−1. The average energy change, enthalpy change and Gibbs energy change for dimer formation in gas phase are −5.9, −3.9 and 8.4kcalmol−1 respectively. Average formation energy change decreased to −13.7kcalmol−1 for dimer–water clusters. The average standard Gibbs energy change of dimer–water cluster formation is positive and observed to be 14.9kcalmol−1. Compared to formation energy changes, relatively large fluctuations were observed with Gibbs energy changes.

Systematic placement of structural water molecules for improved scoring of protein-ligand interactions.

Structural water molecules are found in many protein-ligand complexes. They are known to be vital in mediating hydrogen-bonding interactions and, in some cases, key for facilitating tight binding. It is thus very important to consider water molecules when attempting to model protein-ligand interactions for cognate ligand identification, virtual screening and drug design. While the rigid treatment of water molecules present in structures is feasible, the more relevant task of treating all possible positions and orientations of water molecules with each possible ligand pose is computationally daunting. Current methods in molecular docking provide partial treatment for such water molecules, with modest success. Here we describe a new method employing dead-end elimination to place water molecules within a binding site, bridging interactions between protein and ligand. Dead-end elimination permits a thorough, though still incomplete, treatment of water placement. The results show that this method is able to place water molecules correctly within known complexes and to create physically reasonable hydrogen bonds. The approach has also been incorporated within an inverse molecular design approach, to model a variety of compounds in the process of de novo ligand design. The inclusion of structural water molecules, combined with ranking based on the electrostatic contribution to binding affinity, improves a number of otherwise poor energetic predictions.

CuCl3(H2O)]−complexes aggregated to form hydrate columns in methyl-substituted pyridinium or piperidinium salts

1,2,3-Trimethylpyridinium aquatrichloridocuprate(II), (C(8)H(12)N)[CuCl(3)(H(2)O)], (I), 3,4-dimethylpyridinium aquatrichloridocuprate(II), (C(7)H(10)N)[CuCl(3)(H(2)O)], (II), and 2,3-dimethylpyridinium aquatrichloridocuprate(II), (C(7)H(10)N)[CuCl(3)(H(2)O)], (III), exhibit the same fundamental structure, with (I) and (II) isomorphous and with the unit-cell constants of (III) similar to the reduced unit-cell constants of (I) and (II). The distorted square-planar [CuCl(3)(H(2)O)](-) complex [mirror symmetric in (I) and (II)] forms two semicoordinate Cu···Cl bonds to a neighboring complex to produce a dimer with 2/m symmetry [only inversion symmetry in (III)]. The semicoordinate Cu...Cl bond length of the dimer shows significant elongation at 295 K compared with that at 100 K, while the coordinate Cu-Cl bond lengths are slightly contracted at 295 K compared with those at 100 K. The inorganic dimers are linked by eight hydrogen bonds to four neighboring dimers to establish a checkerboard network layer in the ab plane, with voids between the dimers that accommodate, on both sides, inversion-related organic cation pairs. The organic cations are required by mirror-plane symmetry to be disordered in (I) and (II). The organic cations and [CuCl(3)(H(2)O)](-) complexes are nearly coplanar and tilted out of the layer plane to establish a hybrid organic-inorganic layer structure parallel to (202) [(11-2) in (III)], with hydrate columns (defined by water molecules) and hydrophobic columns (defined by methyl groups) parallel to each other [and along the 2(1) axes in (I) and (II)]. In 1,1-dimethylpiperidinium aquatrichloridocuprate(II), (C(7)H(16)N)[CuCl(3)(H(2)O)], (IV), the bulkier organic cation prevents semicoordinate bonding between complexes, which are hydrogen bonded side-to-side in zigzag chains that place water molecules in columns along half of the 2(1) axes.

A multiscale modelling study of Ni–Cr crack tip initial stage oxidation at different stress intensities

In this study, different scale analyses have been performed to understand the very beginning stage of the Ni–Cr(1 1 1) binary alloy surface oxidation mechanism. The finite elements method (FEM) has been applied to find the stress intensity effect on a compact tension (CT) specimen crack tip, and a 2-μm rectangular region has been prepared for the quasi-continuum (QC) model. The displacement load calculated by FEM was applied at the upper and lower boundaries of the QC model. The obtained atomic positions of the deformed crystal structure were considered for quantum chemical molecular dynamics (QCMD) analysis by placing water molecules on the surface. Water molecules dissociate on the top site followed by the quick diffusion of hydrogen atoms on the surface through the hollow sites. Hydrogen is easily transported into the lattice due to its small atomic size. Increases in stress intensity factor ( K) act to deform the structure, which augments oxygen penetration and reduces hydrogen diffusion time; as a consequence, changes in K result in an increase of metallic surface oxidation. Oxygen preferentially bonds with chromium to develop a protective passive film on the surface, and the quickly diffused hydrogen is trapped on the metal surface. Hydrogen bonds with the metal by receiving electrons and, therefore, works as an oxidant on the surface and weakens the metal atomic bond at the primary stage. Initially, the oxidized surface forms a strong bond with oxygen, resulting in the breakage of metal–metal bonds. Therefore, this hydrogen action enhances the very early stage surface oxidation.

McVol - A program for calculating protein volumes and identifying cavities by a Monte Carlo algorithm

In this paper, we describe a Monte Carlo method for determining the volume of a molecule. A molecule is considered to consist of hard, overlapping spheres. The surface of the molecule is defined by rolling a probe sphere over the surface of the spheres. To determine the volume of the molecule, random points are placed in a three-dimensional box, which encloses the whole molecule. The volume of the molecule in relation to the volume of the box is estimated by calculating the ratio of the random points placed inside the molecule and the total number of random points that were placed. For computational efficiency, we use a grid-cell based neighbor list to determine whether a random point is placed inside the molecule or not. This method in combination with a graph-theoretical algorithm is used to detect internal cavities and surface clefts of molecules. Since cavities and clefts are potential water binding sites, we place water molecules in the cavities. The potential water positions can be used in molecular dynamics calculations as well as in other molecular calculations. We apply this method to several proteins and demonstrate the usefulness of the program. The described methods are all implemented in the program McVol, which is available free of charge from our website at http://www.bisb.uni-bayreuth.de/software.html .

PDB_Hydro: incorporating dipolar solvents with variable density in the Poisson-Boltzmann treatment of macromolecule electrostatics

We describe a new way to calculate the electrostatic properties of macromolecules which eliminates the assumption of a constant dielectric value in the solvent region, resulting in a Generalized Poisson–Boltzmann–Langevin equation (GPBLE). We have implemented a web server () that both numerically solves this equation and uses the resulting water density profiles to place water molecules at preferred sites of hydration. Surface atoms with high or low hydration preference can be easily displayed using a simple PyMol script, allowing for the tentative prediction of the dimerization interface in homodimeric proteins, or lipid binding regions in membrane proteins. The web site includes options that permit mutations in the sequence as well as reconstruction of missing side chain and/or main chain atoms. These tools are accessible independently from the electrostatics calculation, and can be used for other modeling purposes. We expect this web server to be useful to structural biologists, as the knowledge of solvent density should prove useful to get better fits at low resolution for X-ray diffraction data and to computational biologists, for whom these profiles could improve the calculation of interaction energies in water between ligands and receptors in docking simulations.

Simple, intuitive calculations of free energy of binding for protein-ligand complexes. 3. The free energy contribution of structural water molecules in HIV-1 protease complexes.

Structural water molecules within protein active sites are relevant for ligand-protein recognition because they modify the active site geometry and contribute to binding affinity. In this work an analysis of the interactions between 23 ligands and dimeric HIV-1 protease is reported. The X-ray structures of these complexes show the presence of four types of structural water molecules: water 301 (on the symmetry axis), water 313, water 313bis, and peripheral waters. Except for water 301, these are generally complemented with a symmetry-related set. The GRID program was used both for checking water locations and for placing water molecules that appear to be missing from the complexes due to crystallographic uncertainty. Hydropathic analysis of the energetic contributions using HINT indicates a significant improvement of the correlation between HINT scores and the experimentally determined binding constants when the appropriate bridging water molecules are taken into account. In the absence of water r2 = 0.30 with a standard error of +/- 1.30 kcal mol(-1) and when the energetic contributions of the constrained waters are included r2 = 0.61 with a standard error of +/- 0.98 kcal mol(-1). HINT was shown to be able to map quantitatively the contribution of individual structural waters to binding energy. The order of relevance for the various types of water is water 301 > water 313 > water 313bis > peripheral waters. Thus, to obtain the most reliable free energy predictions, the contributions of structural water molecules should be included. However, care must be taken to include the effects of water molecules that add information value and not just noise.

The crystal structure of CCG1/TAF(II)250-interacting factor B (CIB).

The general transcription initiation factor TFIID and its interactors play critical roles in regulating the transcription from both naked and chromatin DNA. We have isolated a novel TFIID interactor that we denoted as CCG1/TAF(II)250-interacting factor B (CIB). We show here that CIB activates transcription. To further understand the function of this protein, we determined its crystal structure at 2.2-Angstroms resolution. The tertiary structure of CIB reveals an alpha/beta-hydrolase fold that resembles structures in the prokaryotic alpha/beta-hydrolase family proteins. It is not similar in structure or primary sequence to any eukaryotic transcription or chromatin factors that have been reported to date. CIB possesses a conserved catalytic triad that is found in other alpha/beta-hydrolases, and our in vitro studies confirmed that it bears hydrolase activity. However, CIB differs from other alpha/beta-hydrolases in that it lacks a binding site excursion, which facilitates the substrate selectivity of the other alpha/beta-hydrolases. Further functional characterization of CIB based on its tertiary structure and through biochemical studies may provide novel insights into the mechanisms that regulate eukaryotic transcription.

Molecular Dynamics Study of Bacteriorhodopsin and the Purple Membrane

Vectorial proton translocation through membranes is a fundamental energy conversion process in biological cells. Bacteriorhodopsin (bR) is a membrane protein that acts as a light-driven, voltage-sensitive proton pump in the purple membrane (PM) of Halobacterium salinarumand achieves its biological function by cycling through a reaction sequence that includes ultrafast (500 fs) events, intermediate (Is) as well as slow (10 ms) steps. bR is of utmost simplicity in comparison with other proton translocating bioenergetic proteins and, therefore, constitutes an ideal model for the study of this process. The PM involves a highly structured supramolecular organization and is fundamental for the in vivo functioning of bR. Over the last 10 years, crystal structures of bR have become available at increasing resolution. The most recent structures resolve many of the lipids of the PM and provide atomic level detail of bR at below 2 A resolution. Fundamental for an understanding of the function of bR is internal water that participates in proton pumping. Several water molecules have been resolved now crystallographically in two channels, on the extracellular and on the intracellular side of bR. We show that free energy perturbation theory can place water molecules in bR, with results that compare well with the observed water molecules, and we apply the method to predict water movement during bR’s photocycle. A preliminary simulation illustrates that water molecules may indeed be displaced during the photocycle, after retinal undergoes an all-trans f 13-cis isomerization, and that this displacement may constitute a mechanism for proton pumping. A key advance reported in this feature article is the integration of the available bR structures into a model for the entire PM. This hexagonally periodic, lamellar model has been hydrated and refined through a constant pressure molecular dynamics simulation. The resulting structure connects extracellular bulk water with water molecules and key side groups in the interior of bR, permitting a seamless overall description of the proton path in the PM, from intracellular to extracellular space. For the first time, a complex cellular reaction can be accounted for in full atomic detail in its complete native environment.

Theoretical pattern of the selective hydration and tautomerization effects on pyridoxal and pyridoxamine 5′-phosphate UV-visible spectra: a tool to band assignment

The geometries of pyridoxamine 5′-phosphate (PMP) tautomers and pyridoxal 5′-phosphate (PLP) Schiff's bases with glycine were optimized at the AMl level. The SCF molecular orbitals and the monoelectronic transitions were calculated using the CNDOL hamiltonian. The most probable transitions in each structure were selected by taking into account the value of their molar absortivity, obtaining a similarity with respect to the experimental data. The influence of the solvent in the electronic spectra was studied by the supermolecular approach, placing water molecules on the most relevant positions. A relation has been found between the band shifts of the spectra and the quantity and position of water molecules in the studied systems. It was determined that the carboxylate and phosphate groups do not have a significant participation in the studied region of the spectrum. The spectrum bands were assigned to possible electronic transitions in various tautomers. The appearance of a band near the 415nm was attributed to those structures that have protonated the imine group, and a hidden band around the 265nm appears when the pyridine nitrogen is protonated.