Examination of the quality of various force fields and solvation models for the equilibrium simulations of GA88 and GB88

Elucidating the relationship between sequence and conformation is essential for the understanding of functions of proteins. While sharing 88 % sequence identity and differing by only seven residues, GA88 and GB88 have completely different structures and serve as ideal systems for investigating the relationship between sequence and function. Benefiting from the continuous advancement of the computational ability of modern computers, molecular dynamics (MD) simulation is now playing an increasingly important role in the study of proteins. However, the reliability of MD simulations is limited by the accuracy of the force fields and solvent model approximations. In this work, several AMBER force fields (AMBER03, AMBER99SB, AMBER12SB, AMBER14SB, AMBER96) and solvent models (TIP3P, IGB5, IGB7, IGB8) have been employed in the simulations of GA88 and GB88. The statistical results from 19 simulations show that GA88 and GB88 both adopt more compact structures than the native structures. GB88 is more stable than GA88 regardless of the force fields and solvent models utilized. Most of the simulations overestimated the salt bridge interaction. The combination of AMBER14SB force field and IGB8 solvent model shows the best overall performance in the simulations of both GA88 and GB88. AMBER03 and AMBER12SB also yield reasonable results but only in the TIP3P explicit solvent model.     

Altered torquoselectivity of fluorine in the iron-tricarbonyl-mediated thermal ring opening of 3-fluorocyclobutene: a density-functional exploration

There are eight possible pathways for the iron-tricarbonyl-assisted thermal electrocyclic ring opening of fluorocyclobutene due to variations in the orientation of the binding of Fe(CO)₃ relative to the fluorine substituent (R₁ or R₂), stereoselectivity (conrotatory or disrotatory, i.e., C or D), and the torquoselectivity of fluorine (inward-facing or outward-facing, i.e., in or out). A density functional study revealed that the energetically favored pathway is R₁ Din. Not only is the D mode favored energetically, but the in configuration was observed to be the lowest-lying mode of R₁, despite the general tendency of fluorine substituents to prefer an out configuration. Data on the activation hardness and aromaticity indices such as BAC and HOMA lead to the same conclusion. However, the R₂ mode surprisingly shows no particular preference for either the Cout or the Dout pathway (i.e., the R₂ mode shows less stereoselectivity than R₁). This behavior occurs due to the influences of both the fluorine substituent and metal coordination. Also, the geminal bond orbitals σ(C–F) and σ*(C–F) appear to participate in ring opening, given the excellent correlation of ?BE with the activation barrier of the transition state.     

TD-M06-2X insights into the absorption and emission spectra of dichlorvos and its molecularly imprinted recognition by methacrylic acid

The absorption and emission spectra of dichlorvos and the dichlorvos-MAA complex in methanol, water, and chloroform in the molecularly imprinted recognition were investigated systematically. The M06-2X results revealed that: 1) the hydroxyl groups in polar solvents such as methanol and water may markedly influence the weak interactions, and then alter the adsorption and emission spectra; 2) the electronic excitation in absorption spectra of dichlorvos is dominated by the configuration HOMO?→?LUMO, but in the most stable dichlorvos-MAA it becomes the ππ* excitation of HOMO?→?LUMO?+?1; 3) Mulliken charges reveal that dichlorvos almost dissociates to Cl^- and a cation in its S₁ excitation state; 4) the phosphorescence spectra of dichlorvos-MAA are relatively weak.

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Graphical Abstract The absorption and emission spectra of dichlorvos and the dichlorvos-MAA complex in the molecularly imprinted recognition of dichlorvos were investigated systematically in methanol, water, and chloroform as solvents.

     

Melt-phase behavior of collapsed PMMA/PVC chains revealed by multiscale simulations

Single- and double-chain models of three stereoregular polymers, iso- and syndiotactic poly(methyl methacrylate) and isotactic poly(vinyl chloride), were extensively simulated using systematic coarse-grained (CG) potentials. It was found that, in vacuum, all of these long chains collapse in a two-stage process from their fully extended configurations into coils, and the two chains in each double-chain model ultimately become intertwined. Strong intermolecular interactions were found to occur between two chains of the same polymer (“like pairs”), which helps to explain the high densities of single-component melts. However, the intermolecular interactions between two chains of different polymers (“unlike pairs”) were stronger than those in like pairs. The enthalpy of mixing for unlike pairs—obtained from their intermolecular interaction energies—was negative, indicating that the two binary blends considered here are homogeneous systems. Moreover, a more negative enthalpy of mixing is suggested to correlate with better miscibility. These results agree well with corresponding experimental and simulated results, once again validating the accuracy of CG potentials when they are used to explore structural and energetic properties. The local structure captured by the isolated long chains dictates the ability to elucidate melt-phase behavior. A scheme involving the preparation of bulk models with initially collapsed chains was proposed; such CG models could be widely used to rapidly screen pairs of polymers for specific applications.

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Graphical Abstract Melt phase behaviors dictated by isolated chains

     

Exploring the cocrystallization potential of urea and benzamide

The cocrystallization landscape of benzamide and urea interacting with aliphatic and aromatic carboxylic acids was studied both experimentally and theoretically. Ten new cocrystals of benzamide were synthesized using an oriented samples approach via a fast dropped evaporation technique. Information about types of known bi-component cocrystals augmented with knowledge of simple binary eutectic mixtures was used for the analysis of virtual screening efficiency among 514 potential pairs involving aromatic carboxylic acids interacting with urea or benzamide. Quantification of intermolecular interaction was achieved by estimating the excess thermodynamic functions of binary liquid mixtures under supercooled conditions within a COSMO-RS framework. The smoothed histograms suggest that slightly more potential pairs of benzamide are characterized in the attractive region compared to urea. Finally, it is emphasized that prediction of cocrystals of urea is fairly direct, while it remains ambiguous for benzamide paired with carboxylic acids. The two known simple eutectics of urea are found within the first two quartiles defined by excess thermodynamic functions, and all known cocrystals are outside of this range belonging to the third or fourth quartile. On the contrary, such a simple separation of positive and negative cases of benzamide miscibility in the solid state is not observed. The difference in properties between urea and benzamide R2,2(8) heterosynthons is also documented by alterations of substituent effects. Intermolecular interactions of urea with para substituted benzoic acid analogues are stronger compared to those of benzamide. Also, the amount of charge transfer from amide to aromatic carboxylic acid and vice versa is more pronounced for urea. However, in both cases, the greater the electron withdrawing character of the substituent, the higher the binding energy, and the stronger the supermolecule polarization via the charge transfer mechanism.     

<Emphasis Type="Italic">Salmonella</Emphasis> in Wild Birds Utilizing Protected and Human Impacted Habitats,Uganda

As human populations in Africa expand, humans encroach and modify wildlife habitats for farming, fishing, tourism, or settlement. Anthropogenic activities in shared environments may promote transmission of zoonotic pathogens between humans, domestic animals, and wildlife. Between July 2012 and February 2014, we evaluated Salmonella prevalence, serovars, genotypes, and antibiotic resistant phenotypes in resident and migratory birds utilizing human-impacted habitats in northwestern Lake Victoria and protected habitats in Queen Elisabeth National Park. Salmonella occurrence in the urban environment was assessed by sampling storm-water and wastewater from a channel that drains Kampala City into Lake Victoria. Salmonella was detected in 4.3% pooled bird fecal samples, and 57.1% of environmental samples. While birds in impacted and protected areas shared serovars, the genotypes were distinct. We found distinct strains in birds and the environment suggesting some strains in birds are host adapted, and strains circulating in the environment may not necessarily disseminate to birds. Conversely, birds in both impacted and protected areas shared strains with the urban environment, suggesting Salmonella disseminates between impacted environments and birds across sites. Overall, more strains were observed in the urban environment compared to birds, and poses risk of Salmonella reemergence in birds and transmission across species and space.     

Increased Morbidity and Mortality in Domestic Animals Eating Dropped and Bitten Fruit in Bangladeshi Villages: Implications for Zoonotic Disease Transmission

We used data on feeding practices and domestic animal health gathered from 207 Bangladeshi villages to identify any association between grazing dropped fruit found on the ground or owners directly feeding bat- or bird-bitten fruit and animal health. We compared mortality and morbidity in domestic animals using a mixed effects model controlling for village clustering, herd size, and proxy measures of household wealth. Thirty percent of household heads reported that their animals grazed on dropped fruit and 20% reported that they actively fed bitten fruit to their domestic herds. Household heads allowing their cattle to graze on dropped fruit were more likely to report an illness within their herd (adjusted prevalence ratio 1.17, 95% CI 1.02–1.31). Household heads directly feeding goats bitten fruit were more likely to report illness (adjusted prevalence ratio 1.35, 95% CI 1.16–1.57) and deaths (adjusted prevalence ratio 1.64, 95% CI 1.13–2.4). Reporting of illnesses and deaths among goats rose as the frequency of feeding bitten fruit increased. One possible explanation for this finding is the transmission of bat pathogens to domestic animals via bitten fruit consumption.