Hydration free energies in the FreeSolv database calculated with polarized iterative Hirshfeld charges

Computer simulations of biomolecular systems often use force fields, which are combinations of simple empirical atom-based functions to describe the molecular interactions. Even though polarizable force fields give a more detailed description of intermolecular interactions, nonpolarizable force fields, developed several decades ago, are often still preferred because of their reduced computation cost. Electrostatic interactions play a major role in biomolecular systems and are therein described by atomic point charges. In this work, we address the performance of different atomic charges to reproduce experimental hydration free energies in the FreeSolv database in combination with the GAFF force field. Atomic charges were calculated by two atoms-in-molecules approaches, Hirshfeld-I and Minimal Basis Iterative Stockholder (MBIS). To account for polarization effects, the charges were derived from the solute’s electron density computed with an implicit solvent model, and the energy required to polarize the solute was added to the free energy cycle. The calculated hydration free energies were analyzed with an error model, revealing systematic errors associated with specific functional groups or chemical elements. The best agreement with the experimental data is observed for the AM1-BCC and the MBIS atomic charge methods. The latter includes the solvent polarization and presents a root-mean-square error of 2.0 kcal mol–1 for the 613 organic molecules studied. The largest deviation was observed for phosphorus-containing molecules and the molecules with amide, ester and amine functional groups

Charge Separation and Isolation in Water and Ice Particles on Strong Impacts

Tarrasó, Olga;Fuente Fuente, Carlos;Reventós, Manue

School intervention to improve mental health of students in Santiago, Chile: a randomized clinical trial.

IMPORTANCE: Depression can have devastating effects unless prevented or treated early and effectively. Schools offer an excellent opportunity to intervene with adolescents presenting emotional problems. There are very few universal school-based depression interventions conducted in low- and middle-income countries. OBJECTIVE: To assess the effectiveness of a school-based, universal psychological intervention to reduce depressive symptoms among adolescents from low-income families. DESIGN, SETTING, AND PARTICIPANTS: A 2-arm, parallel, cluster, randomized clinical trial was conducted in secondary schools in deprived socioeconomic areas of Santiago, Chile. Almost all students registered in the selected schools consented to take part in the study. A total of 2512 secondary school students from 22 schools and 66 classes participated. INTERVENTIONS: Students in the intervention arm attended 11 one-hour weekly and 2 booster classroom sessions of an intervention based on cognitive-behavioral models. The intervention was delivered by trained nonspecialists. Schools in the control arm received the standard school curriculum. MAIN OUTCOMES AND MEASURES: Scores on the self-administered Beck Depression Inventory-II at 3 months (primary) and 12 months (secondary) after completing the intervention. RESULTS: There were 1291 participants in the control arm and 1221 in the intervention arm. Primary outcome data were available for 82.1% of the participants. There was no evidence of any clinically important difference in mean depression scores between the groups (adjusted difference in mean, -0.19; 95% CI, -1.22 to 0.84) or for any of the other outcomes 3 months after completion of the intervention. No significant differences were found in any of the outcomes at 12 months. CONCLUSIONS AND RELEVANCE: A well-designed and implemented school-based intervention did not reduce depressive symptoms among socioeconomically deprived adolescents in Santiago, Chile. There is growing evidence that universal school interventions may not be sufficiently effective to reduce or prevent depressive symptoms. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN19466209

An explicit approach to conceptual density functional theory descriptors of arbitrary order

We present explicit formulas for arbitrary-order derivatives of the energy, grand potential, electron density, and higher-order response functions with respect to the number of electrons, and the chemical potential for any smooth and differentiable model of the energy versus the number of electrons. The resulting expressions for global reactivity descriptors (hyperhardnesses and hypersoftnesses), local reactivity descriptors (hyperFukui functions and local hypersoftnesses), and nonlocal response functions are easy to evaluate computationally. Specifically, the explicit formulas for global/local/nonlocal hypersoftnesses of arbitrary order are derived using Bell polynomials. Explicit expressions for global and local hypersoftness indicators up to fifth order are presented. (C) 2016 Elsevier B.V. All rights reservedVanier-CGS fellowship Ghent University CONACYT FONDECYT 114031

Inter-subunit coupling enables fast CO2-fixation by reductive carboxylases

Enoyl-CoA carboxylases/reductases (ECRs) are some of the most efficient CO2-fixing enzymes described to date. However, the molecular mechanisms underlying the extraordinary catalytic activity of ECRs on the level of the protein assembly remain elusive. Here we used a combination of ambient-temperature X-ray free electron laser (XFEL) and cryogenic synchrotron experiments to study the structural organization of the ECR from Kitasatospora setae. The K. setae ECR is a homotetramer that differentiates into a pair of dimers of open- and closed-form subunits in the catalytically active state. Using molecular dynamics simulations and structure-based mutagenesis, we show that catalysis is synchronized in the K. setae ECR across the pair of dimers. This conformational coupling of catalytic domains is conferred by individual amino acids to achieve high CO2-fixation rates. Our results provide unprecedented insights into the dynamic organization and synchronized inter- and intrasubunit communications of this remarkably efficient CO2-fixing enzyme during catalysis.

Proton transfer in acetaldehyde–water clusters mediated by a single water molecule

Proton transfer in aqueous media is a ubiquitous process, occurring in acid-base chemistry, biology, and in atmospheric photochemistry. Photoionization mass spectrometry coupled with theoretical calculations demonstrate that a relay-type proton transfer mechanism is operational for single-water-molecule-assisted proton transfer between two acetaldehyde molecules in the gas phase. Threshold photoionization of acetaldehyde-water clusters leads to proton transfer between the formyl groups (-CH[double bond, length as m-dash]O) of one acetaldehyde molecule to another, and the subsequent formation of cationic moieties. Density functional theory computations reveal several plausible pathways of proton transfer in mixed cluster cations. Among these pathways, water-mediated proton transfer is energetically favored. Mass spectra and photoionization efficiency curves confirm these theoretical findings and also demonstrate the increased stability of cluster cations where acetaldehyde molecules are symmetrically bonded to the hydronium ion

Pin1 and neurodegeneration: a new player for prion disorders?

Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans conversion of phosphorylated proteins at serine or threonine residues which precede a proline. The peptidyl-prolyl isomerization induces a conformational change of the proteins involved in cell signaling process. Pin1 dysregulation has been associated with some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Proline-directed phosphorylation is a common regulator of these pathologies and a recent work showed that it is also involved in prion disorders. In fact, prion protein phosphorylation at the Ser-43-Pro motif induces prion protein conversion into a disease-associated form. Furthermore, phosphorylation at Ser-43-Pro has been observed to increase in the cerebral spinal fluid of sporadic Creutzfeldt-Jakob Disease patients. These findings provide new insights into the pathogenesis of prion disorders, suggesting Pin1 as a potential new player in the disease. In this paper, we review the mechanisms underlying Pin1 involvement in the aforementioned neurodegenerative pathologies focusing on the potential role of Pin1 in prion disorders

The future of polar organometallic chemistry written in bio-based solvents and water

There is a strong imperative to reduce the release of volatile organic compounds (VOCs) into the environment, and many efforts are currently being made to replace conventional hazardous VOCs in favour of safe, green and bio-renewable reaction media that are not based on crude petroleum. Recent ground-breaking studies from a few laboratories worldwide have shown that both Grignard and (functionalised) organolithium reagents, traditionally handled under strict exclusion of air and humidity and in anhydrous VOCs, can smoothly promote both nucleophilic additions to unsaturated substrates and nucleophilic substitutions in water and other bio-based solvents (glycerol, deep eutectic solvents), competitively with protonolysis, at room temperature and under air. The chemistry of polar organometallics in the above protic media is a complex phenomenon influenced by several factors, and understanding its foundational character is surely stimulating in the perspective of the development of a sustainable organometallic chemistry