The atomistic level structure for the activated human κ-opioid receptor bound to the full Gi protein and the MP1104 agonist.

The kappa opioid receptor (κOR) is an important target for pain therapeutics to reduce depression and other harmful side effects of existing medications. The analgesic activity is mediated by κOR signaling through the adenylyl cyclase-inhibitory family of Gi protein. Here, we report the three-dimensional (3D) structure for the active state of human κOR complexed with both heterotrimeric Gi protein and MP1104 agonist.

Predicted Optimal Bifunctional Electrocatalysts for the Hydrogen Evolution Reaction and the Oxygen Evolution Reaction Using Chalcogenide Heterostructures Based on Machine Learning Analysis of in Silico Quantum Mechanics Based High Throughput Screening.

Two-dimensional van der Waals heterostructure materials, particularly transition metal dichalcogenides (TMDC), have proved to be excellent photoabsorbers for solar radiation, but performance for such electrocatalysis processes as water splitting to form H and O is not adequate. We propose that dramatically improved performance may be achieved by combining two independent TMDC while optimizing such descriptors as rotational angle, bond length, distance between layers, and the ratio of the bandgaps of two component materials. In this paper we apply the least absolute shrinkage and selection operator (LASSO) process of artificial intelligence incorporating these descriptors together with quantum mechanics (density functional theory) to predict novel structures with predicted superior performance.

First-Order Phase Transition in Liquid Ag to the Heterogeneous G-Phase.

A molten metal is an atomic liquid that lacks directional bonding and is free from chemical ordering effects. Experimentally, liquid metals can be undercooled by up to ∼20% of their melting temperature but crystallize rapidly in subnanosecond time scales at deeper undercooling. To address this limited metastability with respect to crystallization, we employed molecular dynamics simulations to study the thermodynamics and kinetics of the glass transition and crystallization in deeply undercooled liquid Ag.

Reply to the 'Comment on "The chemical reactions in electrosprays of water do not always correspond to those at the pristine air-water interface"' by A. J. Colussi and S. Enami, , 2019, , DOI: 10.1039/c9sc00991d.

The air-water interface serves as a crucial site for numerous chemical and physical processes in environmental science and engineering, such as cloud chemistry, ocean-atmosphere exchange, and wastewater treatment. The development of "surface-selective" techniques for probing interfacial properties of water therefore lies at the forefront of research in chemical science. Recently, researchers have adapted electrospray ionization mass spectrometry (ESIMS) to generate microdroplets of water to investigate interfacial phenomena at thermodynamic equilibrium.

Accurate non-bonded potentials based on periodic quantum mechanics calculations for use in molecular simulations of materials and systems.

Molecular dynamics simulations require accurate force fields (FFs) to describe the physical and chemical properties of complex materials and systems. FF parameters for valence interactions can be determined from high-quality Quantum Mechanical (QM) calculations. However, it has been challenging to extract long-range nonbonded interaction potentials from QM calculations since there is no unambiguous method to separate the total QM energy into electrostatics (polarization), van der Waals (vdW), and other components.

Design of a One-Dimensional Stacked Spin Peierls System with Room-Temperature Switching from Quantum Mechanical Predictions.

Planar bis-1,2-dithiolene complex anions of a transition metal (denoted as [M(dithiolato)] and M = Ni, Pd, or Pt ion) favor forming columnar stacks of anions in the crystal that feature S = 1/2 spin-chains, and such a spin-chain compound often undergoes a spin-Peierls-type transition, making this a promising material for conducting and magnetic switching. However, current examples show the transition temperatures are far too low for most applications. We use quantum mechanics to predict that changing the cation arrangement from the boat-type to the chair-type packing configuration in a spin-Peierls-type [Ni(dithiolato)] complex will substantially stabilize the antiferromagnetic coupling, dramatically increasing the transition temperature.

Anomalies in Supercooled Water at ∼230 K Arise from a 1D Polymer to 2D Network Topological Transformation.

Puzzling anomalous properties of water are drastically enhanced in the supercooled region. However, the nature of these anomalies is not known. We report here molecular dynamics simulations using the RexPoN force field from 298 to 200 K along the 1 atm density curve.

Ligand-Modified Boron-Doped Diamond Surface: DFT Insights into the Electronic Properties of Biofunctionalization.

With the increasing power of computation systems, theoretical calculations provide a means for quick determination of material properties, laying out a research plan, and lowering material development costs. One of the most common is Density Functional Theory (DFT), which allows us to simulate the structure of chemical molecules or crystals and their interaction. In developing a new generation of biosensors, understanding the nature of functional linkers, antibodies, and ligands become essential.

Formation of carbon-nitrogen bonds in carbon monoxide electrolysis.

The electroreduction of CO is a promising technology for carbon utilization. Although electrolysis of CO or CO-derived CO can generate important industrial multicarbon feedstocks such as ethylene, ethanol, n-propanol and acetate, most efforts have been devoted to promoting C-C bond formation. Here, we demonstrate that C-N bonds can be formed through co-electrolysis of CO and NH with acetamide selectivity of nearly 40% at industrially relevant reaction rates.

Discovery of Novel Biased Opioid Receptor Ligands through Structure-Based Pharmacophore Virtual Screening and Experiment.

G -protein-biased agonists with minimal β-arrestin recruitment represent opportunities to overcome the serious adverse effects of human mu opioid receptor (μ-OR) agonists and developing alternative and safe treatments for pain. In order to discover novel non-morphinan opioid receptor agonists, we applied hierarchical virtual screening of our in-house database against a pharmacophore based on modeling the active conformations of opioid receptors. We discovered an initial hit compound, a novel μ-OR agonist with a pyrazoloisoquinoline scaffold.

Computational and experimental demonstrations of one-pot tandem catalysis for electrochemical carbon dioxide reduction to methane.

Electroreduction of carbon dioxide to hydrocarbons and oxygenates on copper involves reduction to a carbon monoxide adsorbate followed by further transformation to hydrocarbons and oxygenates. Simultaneous improvement of these processes over a single reactive site is challenging due to the linear scaling relationship of the binding strength of key intermediates. Herein, we report improved electroreduction of carbon dioxide by exploiting a one-pot tandem catalysis mechanism based on computational and electrochemical investigations.

Role of solvent-anion charge transfer in oxidative degradation of battery electrolytes.

Electrochemical stability windows of electrolytes largely determine the limitations of operating regimes of lithium-ion batteries, but the degradation mechanisms are difficult to characterize and poorly understood. Using computational quantum chemistry to investigate the oxidative decomposition that govern voltage stability of multi-component organic electrolytes, we find that electrolyte decomposition is a process involving the solvent and the salt anion and requires explicit treatment of their coupling. We find that the ionization potential of the solvent-anion system is often lower than that of the isolated solvent or the anion.

Interface Structure in Li-Metal/[Pyr][TFSI]-Ionic Liquid System from ab Initio Molecular Dynamics Simulations.

Ionic liquids (ILs) are promising materials for application in a new generation of Li batteries. They can be used as electrolyte or interlayer or incorporated into other materials. ILs have the ability to form a stable solid electrochemical interface (SEI), which plays an important role in protecting the Li-based electrode from oxidation and the electrolyte from extensive decomposition.

Identifying Active Sites for CO Reduction on Dealloyed Gold Surfaces by Combining Machine Learning with Multiscale Simulations.

Gold nanoparticles (AuNPs) and dealloyed AuFe core-shell NP surfaces have been shown to have dramatically improved performance in reducing CO to CO (CO2RR), but the surface features responsible for these improvements are not known. The active sites cannot be identified with surface science experiments, and quantum mechanics (QM) is not practical for the 10 000 surface sites of a 10 nm NP (200 000 bulk atoms). Here, we combine machine learning, multiscale simulations, and QM to predict the performance (-value) of all 5000-10 000 surface sites on AuNPs and dealloyed Au surfaces.

Author Correction: The current state and future directions of RNAi-based therapeutics.

Errors in the alignment and structure of the siRNN and in the structure of the sisiRNA in the original version of Fig. 3 have been corrected.

Dramatic differences in carbon dioxide adsorption and initial steps of reduction between silver and copper.

Converting carbon dioxide (CO) into liquid fuels and synthesis gas is a world-wide priority. But there is no experimental information on the initial atomic level events for CO electroreduction on the metal catalysts to provide the basis for developing improved catalysts. Here we combine ambient pressure X-ray photoelectron spectroscopy with quantum mechanics to examine the processes as Ag is exposed to CO both alone and in the presence of HO at 298 K.

The chemical reactions in electrosprays of water do not always correspond to those at the pristine air-water interface.

The recent application of electrosprays to characterize the air-water interface, along with the reports on dramatically accelerated chemical reactions in aqueous electrosprays, have sparked a broad interest. Herein, we report on complementary laboratory and experiments tracking the oligomerization of isoprene, an important biogenic gas, in electrosprays and isoprene-water emulsions to differentiate the contributions of interfacial effects from those of high voltages leading to charge-separation and concentration of reactants in the electrosprays. To this end, we employed electrospray ionization mass spectrometry, proton nuclear magnetic resonance, calculations and molecular dynamics simulations.

Initial Steps in Forming the Electrode-Electrolyte Interface: HO Adsorption and Complex Formation on the Ag(111) Surface from Combining Quantum Mechanics Calculations and Ambient Pressure X-ray Photoelectron Spectroscopy.

The interaction of water with metal surfaces is at the heart of electrocatalysis. But there remain enormous uncertainties about the atomistic interactions at the electrode-electrolyte interface (EEI). As the first step toward an understanding of the EEI, we report here the details of the initial steps of HO adsorption and complex formation on a Ag(111) surface, based on coupling quantum mechanics (QM) and ambient-pressure X-ray photoelectron spectroscopy (APXPS) experiments.

Electrocatalysis at Organic-Metal Interfaces: Identification of Structure-Reactivity Relationships for CO Reduction at Modified Cu Surfaces.

The limited selectivity of existing CO reduction catalysts and rising levels of CO in the atmosphere necessitate the identification of specific structure-reactivity relationships to inform catalyst development. Herein, we develop a predictive framework to tune the selectivity of CO reduction on Cu by examining a series of polymeric and molecular modifiers. We find that protic species enhance selectivity for H, hydrophilic species enhance formic acid formation, and cationic hydrophobic species enhance CO selectivity.

Publisher Correction: The current state and future directions of RNAi-based therapeutics.

The use of the names for patisiran has been made consistent throughout the article in line with the journal style and typographical errors have been corrected.

Reaction intermediates during operando electrocatalysis identified from full solvent quantum mechanics molecular dynamics.

Electrocatalysis provides a powerful means to selectively transform molecules, but a serious impediment in making rapid progress is the lack of a molecular-based understanding of the reactive mechanisms or intermediates at the electrode-electrolyte interface (EEI). Recent experimental techniques have been developed for operando identification of reaction intermediates using surface infrared (IR) and Raman spectroscopy. However, large noises in the experimental spectrum pose great challenges in resolving the atomistic structures of reactive intermediates.

The current state and future directions of RNAi-based therapeutics.

The RNA interference (RNAi) pathway regulates mRNA stability and translation in nearly all human cells. Small double-stranded RNA molecules can efficiently trigger RNAi silencing of specific genes, but their therapeutic use has faced numerous challenges involving safety and potency. However, August 2018 marked a new era for the field, with the US Food and Drug Administration approving patisiran, the first RNAi-based drug.