Multipose Binding in Molecular Docking

Molecular docking has been extensively applied in virtual screening of small molecule libraries for lead identification and optimization. A necessary prerequisite for successful differentiation between active and non-active ligands is the accurate prediction of their binding affinities in the complex by use of docking scoring functions. However, many studies have shown rather poor correlations between docking scores and experimental binding affinities. Our work aimed to improve this correlation by implementing a multipose binding concept in the docking scoring scheme. Multipose binding, i.e., the property of certain protein-ligand complexes to exhibit different ligand binding modes, has been shown to occur in nature for a variety of molecules. We conducted a high-throughput docking study and implemented multipose binding in the scoring procedure by considering multiple docking solutions in binding affinity prediction. In general, improvement of the agreement between docking scores and experimental data was observed, and this was most pronounced in complexes with large and flexible ligands and high binding affinities. Further developments of the selection criteria for docking solutions for each individual complex are still necessary for a general utilization of the multipose binding concept for accurate binding affinity prediction by molecular docking.     

Revamping SiO2 Spheres by Core–Shell Porosity Endowment to Construct a Mazelike Nanoreactor for Enhanced Catalysis in CO2 Hydrogenation to Methanol

Beyond the catalytic activity of nanocatalysts, the support with architectural design and explicit boundary could also promote the overall performance through improving the diffusion process, highlighting additional support for the morphology-dependent activity. To delineate this, herein, a novel mazelike-reactor framework, namely multi-voids mesoporous silica sphere (MVmSiO₂), is carved through a top-down approach by endowing core-shell porosity premade Stöber SiO₂ spheres. The precisely-engineered MVmSiO₂ with peripheral one-dimensional pores in the shell and interconnecting compartmented voids in the core region is simulated to prove combined hierarchical and structural superiority over its analogous counterparts. Supported with CuZn-based alloys, mazelike MVmSiO₂ nanoreactor experimentally demonstrated its expected workability in model gas-phase CO₂ hydrogenation reaction where enhanced CO₂ activity, good methanol yield, and more importantly, a prolonged stable performance are realized. While tuning the nanoreactor composition besides morphology optimization could further increase the catalytic performance, it is accentuated that the morphological architecture of support further boosts the reaction performance apart from comprehensive compositional optimization. In addition to the found morphological restraints and size-confinement effects imposed by MVmSiO₂, active sites of catalysts are also investigated by exploring the size difference of the confined CuZn alloy nanoparticles in CO₂ hydrogenation employing both in-situ experimental characterizations and density functional theory calculations.     

Peculiar electric properties of polarized layer in alkaline silicate glasses

Broadband dielectric spectroscopy (BDS) was applied to study polarization phenomena in alkaline silicate glasses, in particular, properties and structure of subsurface (anodic) polarized layers forming in poling with deposited film electrodes of different structures. A model of poled glasses which does not contradict experimental data is proposed. In accordance with the model, a poled glass is presented as two resistor-capacitor circuits in a series connection, one of which is the polarized layer and another is the rest of the sample. It is found that the electric properties of the layers essentially depend on the structure of the anodic electrode used in glass poling. It is also shown that the dielectric response of poled glass samples is mainly determined by the electric properties of the submicron polarized layers and this gives an opportunity to reveal specific properties of the layers rather than ones of the glass sample bulk. Revealed temperature dependence of DC conductivity of the polarized layers obeys Arrhenius's law, and determining activation energy does not depend on the electrode. Finally, it is noted that today above-mentioned information about polarized layers can be obtained only by BDS.     

Cognitive Mapping and Planning for Visual Navigation

International Journal of Computer Vision - We introduce a neural architecture for navigation in novel environments. Our proposed architecture learns to map from first-person views and plans a...     

Microstructure and mechanical properties of Mg-5Li-1Al sheets prepared by accumulative roll bonding

Ultrafine-grain and high-strength Mg-5Li-1Al sheets were prepared by accumulative roll bonding (ARB) process. Evolution of microstructure and mechanical properties of ARB-processed Mg-5Li-1Al sheets was investigated.Results show that, during ARB process, the evolution of deformation mechanism of t Mg-5Li-1Al alloy is as follows: twinning deformation, shear deformation, forming macro shear zone, and finally dynamic recrystallization (DRX). The grain refining mechanism changes from twin DRX to rotation DRX. With the increase in ARB cycles, strength of the Mg-5Li-1Al sheets is enhanced, whilst elongation varies slightly. With the increase in rolling cycles, anisotropy of mechanical properties decreases. It is conclusive that strain hardening and grain refinement dominate the strengthening mechanism of Mg-5Li-1Al alloy.     

Structure and Properties of High-Temperature Multilayer Hybrid Material Based on Vanadium Alloy and Stainless Steel

The present work is devoted to the development of new structural composite material having the unique complex of properties for operating in ultrahard conditions that combine high temperatures, radiation, and aggressive environments. A new three-layer composite tube material based on vanadium alloy (V-4Ti-4Cr) protected by stainless steel (Fe-0.2C-13Cr) has been obtained by co-extrusion. Mechanism and kinetics of formation as well as structure, composition, and mechanical properties of “transition” area between vanadium alloy and stainless steel have been studied. The transition area (13- to 22-µm thick) of the diffusion interaction between vanadium alloy and steel was formed after co-extrusion. The microstructure in the transition area was rather complicated comprising different grain sizes in components, but having no defects or brittle phases. Tensile strength of the composite was an average 493 ± 22 MPa, and the elongation was 26 ± 3 pct. Annealing at 1073 K (800 °C) increased the thickness of transition area up to 1.2 times, homogenized microstructure, and slightly changed mechanical properties. Annealing at 1273 K (1000 °C) further increased the thickness of transition area and also lead to intensive grain growth in steel and sometimes to separation between composite components during tensile tests. Annealing at 1073 K (800 °C) is proposed as appropriate heat treatment after co-extrusion of composite providing balance between diffusion interaction thickness and microstructure and monolithic-like behavior of composite during tensile tests.

     

Numerical study of the near-field of highly underexpanded turbulent gas jets

For safety issues related to the storage of gases (e.g. hydrogen) under high pressure, it is necessary to determine how the gas is released in the case of failure. In particular, there exist limited quantitative information on the near-field properties of gas jets, which are important for establishing proper decay laws in the far-field. Simulations of the near-field of highly underexpanded (high pressure) gas jets have been performed using Finite-Volume solver of the CAST3M code and validated using several sources available in the literature. The numerical model solves the 3D Compressible Multi-Component Navier–Stokes equations directly without relying on the compressibility-corrected turbulence models. It provides sufficiently fair mean predictions both in the case of one-component air–air and two-component helium-air releases. Possible initial conditions for the far-field simulations are suggested in terms of distance from the source, as well as the turbulence characteristics and gas-dynamic parameters at this location. In addition, these results are used to evaluate several notional nozzle concepts in order to determine the one physically consistent.