Dissociation of Water at Iron Surfaces: Generalized Gradient Functional and Range-Separated Hybrid Functional Study

Interaction of water with iron surface is involved in many significant processes like corrosion and water treatment by zerovalent iron nanoparticles (nZVI). We used a density functional theory to study adsorption and chemical reaction of a single water molecule with two low-index surfaces of iron, Fe(100) and Fe(111). We used generalized gradient form (PW91) of the density functional and also range-separated hybrid functional (HSE06), which incorporates a fraction of the Hartree–Fock exchange. A water molecule adsorbs on both surfaces with oxygen atom pointing on top a Fe atom and has higher affinity to the Fe(111) surface. The adsorbed water molecule can dissociate into H + OH (H–Fe–OH) species attached to the Fe surface with an activation barrier of 15.7 and 13.3 kcal/mol for the (100) and (111) surface, respectively. The hybrid functional yields similar energies for adsorption but predicts higher dissociation barriers compared to the generalized gradient functional. The HSE06 calculation reveals that H–Fe–OH is a deep minimum on the reaction profile of the studied process, in particular on the Fe(111) surface. This indicates that dissociated species can play an important role in reactivity of nZVI with pollutants in water treatment. The HSE06 functional also improves the overall agreement between theoretical calculations and previous experimental studies of the adsorption of water on iron surfaces

Band Gaps and Optical Spectra of Chlorographene, Fluorographene and Graphane from G₀W₀, GW₀ and GW Calculations on Top of PBE and HSE06 Orbitals

The band structures of three graphene derivatives (chlorographene, fluorographene, and graphane) were analyzed at three levels of many-body GW theory (G₀W₀, GW₀, and GW) constructed over GGA (PBE) and screened hybrid HSE06 orbitals. DFT band gap values obtained with the HSE06 functional were notably larger than those from PBE calculations but were significantly lower than band gaps from all GW calculations. On the other hand, all GW-type calculations gave similar band gaps despite some differences in band structures. The band gap (4.9 eV at the highest GW-HSE06 level) was predicted to be smaller than that of fluorographene (8.3 eV) or graphane (6.2 eV). However, chlorographene can be considered a wide-band gap insulator analogous to fluorographene and graphane. Using the Bethe–Salpeter equation, optical absorptions of graphene derivatives were found to be at significantly lower energies due to large binding energies of excitons (1.3, 1.9, and 1.5 eV for chlorographene, fluorographene, and graphane, respectively). Point defects lowered band gaps and absorption energies. Taking into account the low concentration of defects in this type of material, their effect on the discussed electronic properties was rather small

The complexity of the nursing work in hospiatl for custody and psychiatric treatment

Objetivo: analisar as formas com que os profissionais de enfermagem lidam com a complexidade do trabalho no Hospital de Custódia e Tratamento Psiquiátrico. Métodos: pesquisa qualitativa descritiva, tendo como sujeitos 15 trabalhadores de enfermagem. A coleta de dados se deu por intermédio da entrevista semiestruturada e análise temática de conteúdo. Resultados: a principal estratégia de proteção e prevenção à saúde do trabalhador foi a interdisciplinaridade nas ações. Conclusão: evidenciou-se a necessidade de medidas educativas voltadas para a definição do papel do Hospital de Custódia na sociedade e na vida dos psicóticos infratores, e a reestruturação da organização do trabalho de forma interdisciplinar, a fim de que este se converta em possibilidades de criação e realização para o trabalhador, no que diz respeito ao seu aparelho físico e psíquico

Convergence of Free Energy Profile of Coumarin in Lipid Bilayer

Atomistic molecular dynamics (MD) simulations of druglike molecules embedded in lipid bilayers are of considerable interest as models for drug penetration and positioning in biological membranes. Here we analyze partitioning of coumarin in dioleoylphosphatidylcholine (DOPC) bilayer, based on both multiple, unbiased 3 μs MD simulations (total length) and free energy profiles along the bilayer normal calculated by biased MD simulations (∼7 μs in total). The convergences in time of free energy profiles calculated by both umbrella sampling and z-constraint techniques are thoroughly analyzed. Two sets of starting structures are also considered, one from unbiased MD simulation and the other from “pulling” coumarin along the bilayer normal. The structures obtained by pulling simulation contain water defects on the lipid bilayer surface, while those acquired from unbiased simulation have no membrane defects. The free energy profiles converge more rapidly when starting frames from unbiased simulations are used. In addition, z-constraint simulation leads to more rapid convergence than umbrella sampling, due to quicker relaxation of membrane defects. Furthermore, we show that the choice of RESP, PRODRG, or Mulliken charges considerably affects the resulting free energy profile of our model drug along the bilayer normal. We recommend using z-constraint biased MD simulations based on starting geometries acquired from unbiased MD simulations for efficient calculation of convergent free energy profiles of druglike molecules along bilayer normals. The calculation of free energy profile should start with an unbiased simulation, though the polar molecules might need a slow pulling afterward. Results obtained with the recommended simulation protocol agree well with available experimental data for two coumarin derivatives

Effect of Lipid Charge on Membrane Immersion of Cytochrome P450 3A4

Microsomal cytochrome P450 enzymes (CYPs) are membrane-attached enzymes that play indispensable roles in biotransformations of numerous endogenous and exogenous compounds. Although recent progress in experiments and simulations has allowed many important features of CYP–membrane interactions to be deciphered, many other aspects remain underexplored. Using microsecond-long molecular dynamics simulations, we analyzed interaction of CYP3A4 with bilayers composed of lipids differing in their polar head groups, i.e., phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. In the negatively charged lipids, CYP3A4 was immersed more deeply and was more inclined toward the membrane because of favorable electrostatic and hydrogen bonding interactions between the CYP catalytic domain and lipid polar head groups. We showed that electrostatics significantly contributes to positioning and orientation of CYP on the membrane and might contribute to the experimentally observed preferences of individual CYP isoforms to distribute in (dis)­ordered membrane microdomains

Behavior of Human Cytochromes P450 on Lipid Membranes

Human cytochromes P450 (CYPs) are membrane-anchored enzymes involved in biotransformation of many marketed drugs. We constructed atomic models of six human CYPs (CYP1A2, 2A6, 2C9, 2D6, 2E1, and 3A4) anchored to a lipid bilayer to investigate the positions and orientations of CYPs on a membrane. We equilibrated the models by molecular dynamics simulations on a 100+ ns time scale. Catalytic domains of all studied CYPs were found to be partially immersed in the lipid bilayer, whereas the N-terminal part and F′/G′ loop are deeply immersed. The proximal side of the enzyme faces the cytosol, whereas the distal side, where openings of substrate access and product release channels to the active site are primarily located, points toward the lipid bilayer. Access channels with openings in the vicinity of the B/C and F/G loops are typically positioned below the lipid head groups, whereas the solvent channel points toward the membrane–water interface. We found that the access channel opening positions match the preferred substrate positions, whereas the product release channel exit positions correspond closely with the positions of the products. This may indicate that membrane-anchored CYPs have evolutionarily adapted to facilitate uptake of nonpolar substrates from the membrane and uptake/release of polar substrates or products from/to the membrane–water interface

Explicit Water Models Affect the Specific Solvation and Dynamics of Unfolded Peptides While the Conformational Behavior and Flexibility of Folded Peptides Remain Intact

Conventional molecular dynamics simulations on 50 ns to 1 μs time scales were used to study the effects of explicit solvent models on the conformational behavior and solvation of two oligopeptide solutes: α-helical EK-peptide (14 amino acids) and a β-hairpin chignolin (10 amino acids). The widely used AMBER force fields (ff99, ff99SB, and ff03) were combined with four of the most commonly used explicit solvent models (TIP3P, TIP4P, TIP5P, and SPC/E). Significant differences in the specific solvation of chignolin among the studied water models were identified. Chignolin was highly solvated in TIP5P, whereas reduced specific solvation was found in the TIP4P, SPC/E, and TIP3P models for kinetic, thermodynamic, and both kinetic and thermodynamic reasons, respectively. The differences in specific solvation did not influence the dynamics of structured parts of the folded peptide. However, substantial differences between TIP5P and the other models were observed in the dynamics of unfolded chignolin, stability of salt bridges, and specific solvation of the backbone carbonyls of EK-peptide. Thus, we conclude that the choice of water model may affect the dynamics of flexible parts of proteins that are solvent-exposed. On the other hand, all water models should perform similarly for well-structured folded protein regions. The merits of the TIP3P model include its high and overestimated mobility, which accelerates simulation processes and thus effectively increases sampling

A- to B‑DNA Transition in AMBER Force Fields and Its Coupling to Sugar Pucker

The A/B transition is a basic element of DNA conformational change. Because of its involvement in the sensing of the ionic conditions by DNA and in specific protein–DNA interactions, this transition is important for biological functions of DNA. Therefore, accurate modeling of the A/B equilibrium by means of empirical force fields is of utmost interest. In this work, we examine the A/B equilibrium in three AMBER force fields, including the recent bsc1 and OL15 modifications, using much longer MD simulations than attempted before. Special attention is paid to the coupling of the A/B equilibrium with the south/north (S/N) transition of the sugar pucker. We found that none of the tested force fields provided a satisfactory description of the A/B equilibrium because the B-form was predicted to be much too stable and the A-form was predicted to be almost absent even in concentrated trifluoroethanol solutions. Based on comparison with NMR data for duplexes and single nucleosides, we hypothesize that this problem arose from the incorrect description of the S/N equilibrium of sugar pucker, where the south conformation is much too stable, thus stabilizing the B-form. Because neither the A/B equilibrium in duplexes nor the S/N equilibrium in nucleosides was described accurately, further refinements of the AMBER DNA force fields are needed

Effect of Guanine to Inosine Substitution on Stability of Canonical DNA and RNA Duplexes: Molecular Dynamics Thermodynamics Integration Study

Guanine to inosine (G → I) substitution has often been used to study various properties of nucleic acids. Inosine differs from guanine only by loss of the N2 amino group, while both bases have similar electrostatic potentials. Therefore, G → I substitution appears to be optimally suited to probe structural and thermodynamics effects of single H-bonds and atomic groups. However, recent experiments have revealed substantial difference in free energy impact of G → I substitution in the context of B-DNA and A-RNA canonical helices, suggesting that the free energy changes reflect context-dependent balance of energy contributions rather than intrinsic strength of a single H-bond. In the present study, we complement the experiments by free energy computations using thermodynamics integration method based on extended explicit solvent molecular dynamics simulations. The computations successfully reproduce the basic qualitative difference in free energy impact of G → I substitution in B-DNA and A-RNA helices although the magnitude of the effect is somewhat underestimated. The computations, however, do not reproduce the salt dependence of the free energy changes. We tentatively suggest that the different effect of G → I substitution in A-RNA and B-DNA may be related to different topologies of these helices, which affect the electrostatic interactions between the base pairs and the negatively charged backbone. Limitations of the computations are briefly discussed

Coarse-Grain Simulations of Skin Ceramide NS with Newly Derived Parameters Clarify Structure of Melted Phase

Ceramides are lipids that are involved in numerous biologically important structures (e.g., the stratum corneum and ceramide-rich platforms) and processes (e.g., signal transduction and membrane fusion), but their behavior is not fully understood. We report coarse-grain force field parameters for <i>N</i>-lignocerylsphingosine (ceramide NS, also known as ceramide 2) that are consistent with the Martini force field. These parameters were optimized for simulations in the gel phase and validated against atomistic simulations. Coarse-grained simulations with our parameters provide areas per lipid, membrane thicknesses, and electron density profiles that are in good agreement with atomistic simulations. Properties of the simulated membranes are compared with available experimental data. The obtained parameters were used to model the phase behavior of ceramide NS as a function of temperature and hydration. At low water content and above the main phase transition temperature, the bilayer melts into an irregular phase, which may correspond to the unstructured melted-chain phase observed in X-ray diffraction experiments. The developed parameters also reproduce the extended conformation of ceramide, which may occur in the stratum corneum. The parameters presented herein will facilitate studies on important complex functional structures such as the uppermost layer of the skin and ceramide-rich platforms in phospholipid membranes