Toward Fully Automated High Performance Computing Drug Discovery: A Massively Parallel Virtual Screening Pipeline for Docking and Molecular Mechanics/Generalized Born Surface Area Rescoring to Improve Enrichment

In this work we announce and evaluate a high throughput virtual screening pipeline for <i>in-silico</i> screening of virtual compound databases using high performance computing (HPC). Notable features of this pipeline are an automated receptor preparation scheme with unsupervised binding site identification. The pipeline includes receptor/target preparation, ligand preparation, VinaLC docking calculation, and molecular mechanics/generalized Born surface area (MM/GBSA) rescoring using the GB model by Onufriev and co-workers [<i>J. Chem. Theory Comput.</i> <b>2007</b>, <i>3</i>, 156–169]. Furthermore, we leverage HPC resources to perform an unprecedented, comprehensive evaluation of MM/GBSA rescoring when applied to the DUD-E data set (Directory of Useful Decoys: Enhanced), in which we selected 38 protein targets and a total of ∼0.7 million actives and decoys. The computer wall time for virtual screening has been reduced drastically on HPC machines, which increases the feasibility of extremely large ligand database screening with more accurate methods. HPC resources allowed us to rescore 20 poses per compound and evaluate the optimal number of poses to rescore. We find that keeping 5–10 poses is a good compromise between accuracy and computational expense. Overall the results demonstrate that MM/GBSA rescoring has higher average receiver operating characteristic (ROC) area under curve (AUC) values and consistently better early recovery of actives than Vina docking alone. Specifically, the enrichment performance is target-dependent. MM/GBSA rescoring significantly out performs Vina docking for the folate enzymes, kinases, and several other enzymes. The more accurate energy function and solvation terms of the MM/GBSA method allow MM/GBSA to achieve better enrichment, but the rescoring is still limited by the docking method to generate the poses with the correct binding modes

Crystallization Behavior of Poly(ethylene oxide) in Vertically Aligned Carbon Nanotube Array

We investigate the effect of the presence of vertically aligned multiwalled carbon nanotubes (CNTs) on the orientation of poly­(ethylene oxide) (PEO) lamellae and PEO crystallinity. The high alignment of carbon nanotubes acting as templates probably governs the orientation of PEO lamellae. This templating effect might result in the lamella planes of PEO crystals oriented along a direction parallel to the long axis of the nanotubes. The presence of aligned carbon nanotubes also gives rise to the decreases in PEO crystallinity, crystallization temperature, and melting temperature due to the perturbation of carbon nanotubes to the crystallization of PEO. These effects have significant implications for controlling the orientation of PEO lamellae and decreasing the crystallinity of PEO and thickness of PEO lamellae, which have significant impacts on ion transport in PEO/CNT composite and the capacitive performance of PEO/CNT composite. Both the decreased PEO crystallinity and the orientation of PEO lamellae along the long axes of vertically aligned CNTs give rise to the decrease in the charge transfer resistance, which is associated with the improvements in the ion transport and capacitive performance of PEO/CNT composite

Additional file 2: Table S4a. of Different survival analysis methods for measuring long-term outcomes of Indigenous and non-Indigenous Australian cancer patients in the presence and absence of competing risks

Regression analysis of time trend after diagnosis using cause-specific mortality (Cox proportional hazard regression), relative survival (Poisson regression), and competing risk analysis (Fine-Gray regression), all cancers combined1, Australia NT, 1991–2009 (full model). Description: Table S4a. including hazard ratios for specific cancer sites. (DOC 47 kb

Additional file 1: Table S3a. of Different survival analysis methods for measuring long-term outcomes of Indigenous and non-Indigenous Australian cancer patients in the presence and absence of competing risks

Regression analysis of cause-specific mortality (Cox proportional hazard regression), relative survival (Poisson regression), and competing risk (Fine-Gray regression), all cancers combined1, Australia NT, 1991–2009 (full model). Description: Table S3a. including hazard ratios for specific cancer sites. (DOC 49 kb

Temporal Changes and Stereoisomeric Compositions of 1,2,5,6,9,10-Hexabromocyclododecane and 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane in Marine Mammals from the South China Sea

Stereoisomeric compositions of 1,2,5,6,9,10-hexabromocyclododecane (HBCD) and 1,2-dibromo-4-(1,2-dibromoethyl)­cyclohexane (TBECH) were investigated in the blubber of two species of marine mammals, finless porpoises (<i>Neophocaena phocaenoides</i>) and Indo-Pacific humpback dolphins (<i>Sousa chinensis</i>), from the South China Sea between 2005 and 2015. The concentrations of ΣHBCD in samples of porpoise (<i>n</i> = 59) and dolphin (<i>n</i> = 32) ranged from 97.2 to 6,260 ng/g lipid weight (lw) and from 447 to 45,800 ng/g lw, respectively, while those of ΣTBECH were both roughly 2 orders of magnitude lower. A significant increasing trend of ΣHBCD was found in dolphin blubber over the past decade. The diastereomeric profiles exhibited an absolute predominance of α-HBCD (mostly >90%), while the proportions of four TBECH diastereomers in the samples appeared similar. A preferential enrichment of the (−)-enantiomers of α-, β-, and γ-HBCD was found in most blubber samples. Interestingly, the body lengths of porpoises showed a significant negative correlation with the enantiomer fractions of α-HBCD. Significant racemic deviations were also observed for α-, γ-, and δ-TBECH enantiomeric pairs. This is the first report of the presence of TBECH enantiomers in the environment. The estimated hazard quotient indicates that there is a potential risk to dolphins due to HBCD exposure

Capillary Effect-Enabled Water Electrolysis for Enhanced Electrochemical Ozone Production by Using Bulk Porous Electrode

A significant overpotential necessary for the electrochemical oxygen evolution reaction (OER) is one of the most serious disadvantages in water electrolysis, which, on the contrary, gives the probability to electrochemically produce ozone alternative to the common corona discharge. To effectively suppress the competitive OER and improve gaseous ozone escaping, here we present a capillary effect-enabled electrolysis strategy by employing an unusual partial-submersed mode of anode composed of a β-PbO₂ cuboids-loaded bulk porous Pb, and realize a much enhanced electrocatalytic gaseous ozone production in comparison to the cases of solid Pb counterpart and/or usual submersion operation. Detailed study reveals a capillary pressure-induced “molecular oxygen-locking effect” in the electrolyte fully filled in the porous structure of the electrode area above the electrolyte pool level, which unexpectedly leads to the production of unusual ·O₃^– intermediate. Distinctive from the traditional electrochemical ozone production (EOP) mechanism dependent on the essential reaction between the atomic oxygen and molecular oxygen, the ·O₃^– intermediate generation favors the EOP process in the special case where the capillary action is relevant for a porous bulk anode

Intrinsic Ferromagnetism in 2D Fe₂H with a High Curie Temperature

The rational design of ferromagnetic materials is crucial for the development of spintronic devices. Using first-principles structural search calculations, we have identified 73 two-dimensional transition metal hydrides. Some of them show interesting magnetic properties, even when combined with the characteristics of the electrides. In particular, the P3̅m1 Fe2H monolayer is stabilized in a 1T-MoS2-type structure with a local magnetic moment of 3 μB per Fe atom, whose robust ferromagnetism is attributed to the exchange interaction between neighboring Fe atoms within and between sublayers, leading to a remarkably high Curie temperature of 340 K. On the other hand, it has a large magnetic anisotropic energy and spin-polarization ratio. Interestingly, the above room-temperature ferromagnetism of the Fe2H monolayer is well preserved within a biaxial strain of 5%. The structure and electron property of surface-functionalized Fe2H are also explored. All of these interesting properties make the Fe2H monolayer an attractive candidate for spintronic nanodevices

Low-Temperature Synthesis of Mesoporous Half-Metallic High-Entropy Spinel Oxide Nanofibers for Photocatalytic CO₂ Reduction

High-entropy oxides (HEOs) exhibit great prospects owing to their varied composition, chemical adaptability, adjustable light-absorption ability, and strong stability. In this study, we report a strategy to synthesize a series of porous high-entropy spinel oxide (HESO) nanofibers (NFs) at a low temperature of 400 °C by a sol–gel electrospinning technique. The key lies in selecting six acetylacetonate salt precursors with similar coordination abilities, maintaining a high-entropy disordered state during the transformation from stable sols to gel NFs. The as-synthesized HESO NFs of (NiCuMnCoZnFe)3O4 show a high specific surface area of 66.48 m2/g, a diverse elemental composition, a dual bandgap, half-metallicity property, and abundant defects. The diverse elements provide various synergistic catalytic sites, and oxygen vacancies act as active sites for electron–hole separation, while the half-metallicity and dual-bandgap structure offer excellent light absorption ability, thus expanding its applicability to a wide range of photocatalytic processes. As a result, the HESO NFs can efficiently convert CO2 into CH4 and CO with high yields of 8.03 and 15.89 μmol g–1 h–1, respectively, without using photosensitizers or sacrificial agents

Low-Temperature Synthesis of Mesoporous Half-Metallic High-Entropy Spinel Oxide Nanofibers for Photocatalytic CO₂ Reduction

High-entropy oxides (HEOs) exhibit great prospects owing to their varied composition, chemical adaptability, adjustable light-absorption ability, and strong stability. In this study, we report a strategy to synthesize a series of porous high-entropy spinel oxide (HESO) nanofibers (NFs) at a low temperature of 400 °C by a sol–gel electrospinning technique. The key lies in selecting six acetylacetonate salt precursors with similar coordination abilities, maintaining a high-entropy disordered state during the transformation from stable sols to gel NFs. The as-synthesized HESO NFs of (NiCuMnCoZnFe)3O4 show a high specific surface area of 66.48 m2/g, a diverse elemental composition, a dual bandgap, half-metallicity property, and abundant defects. The diverse elements provide various synergistic catalytic sites, and oxygen vacancies act as active sites for electron–hole separation, while the half-metallicity and dual-bandgap structure offer excellent light absorption ability, thus expanding its applicability to a wide range of photocatalytic processes. As a result, the HESO NFs can efficiently convert CO2 into CH4 and CO with high yields of 8.03 and 15.89 μmol g–1 h–1, respectively, without using photosensitizers or sacrificial agents