Study of Tamiflu sensitivity to variants of A/H5N1 virus using different force fields

An accurate estimation of binding free energy of a ligand to receptor ΔG(bind) is one of the most important problems in drug design. The success of solution of this problem is expected to depend on force fields used for modeling a ligand-receptor complex. In this paper, we consider the impact of four main force fields, AMBER99SB, CHARMM27, GROMOS96 43a1, and OPLS-AA/L, on the binding affinity of Oseltamivir carboxylate to the wild-type and Y252H, N294S, and H274Y mutants of glycoprotein neuraminidase from the pandemic A/H5N1 virus. Having used the molecular mechanic-Poisson-Boltzmann surface area method, we have shown that ΔG(bind), obtained by AMBER99SB, OPLS-AA/L, and CHARMM27, shows the high correlation with the available experimental data. They correctly capture the binding ranking Y252H → WT → N294S → H274Y observed in experiments (Collins, P. J. et al. Nature 2008, 453, 1258). In terms of absolute values of binding scores, results obtained by AMBER99SB are in the nearest range with experiments, while OPLS-AA/L, which is applied to study binding of Oseltamivir to the influenza virus for the first time, gives rather big negative values for ΔG(bind). GROMOS96 43a1 provides a lower correlation as it supports Oseltamivir to be more resistant to N294S than H274Y. Our study suggests that force fields have pronounced influence on theoretical estimations of binding free energy of a ligand to receptor. The effect of all-atom models on dynamics of the binding pocket as well as on the hydrogen-bond network between Oseltamivir and receptors is studied in detail. The hydrogen network, obtained by GROMOS, is weakest among four studied force fields.     

On a fixed-point theorem

Institute of Mathematics, Hanoi. Translated from Funktsional'nyi Analiz i Ego Prilozheniya, Vol. 30, No. 3, pp. 93–94, July–September, 1996.     

The Bhattacharya Function of Complete Monomial Ideals in Two Variables

We give explicit formulas for the Bhattacharya function of 𝔪-primary complete monomial ideals in two variables in terms of the vertices of the Newton polyhedra or in terms of the decompositions of the ideals as products of simple ideals.     

Facile synthesis of SnO2–ZnO core–shell nanowires for enhanced ethanol-sensing performance

The design of core–shell heteronanostructures is powerful tool to control both the gas selectivity and the sensitivity due to their hybrid properties. In this work, the SnO₂–ZnO core–shell nanowires (NWs) were fabricated via two-step process comprising the thermal evaporation of the single crystalline SnO₂ NWs core and the spray-coating of the grainy polycrystalline ZnO shell for enhanced ethanol sensing performance. The as-obtained products were investigated by X-ray diffraction, scanning electron microscopy, and photoluminescence. The ethanol gas-sensing properties of pristine SnO₂ and ZnO–SnO₂ core–shell NW sensors were studied and compared. The gas response to 500 ppm ethanol of the core–shell NW sensor increased to 33.84, which was 12.5-fold higher than that of the pristine SnO₂ NW sensor. The selectivity of the core–shell NW sensor also improved. The response to 100 ppm ethanol was about 14.1, whereas the response to 100 ppm liquefied petroleum gas, NH₃, H₂, and CO was smaller, and ranged from 2.5 to 5.3. This indicates that the core–shell heterostructures have great potential for use as gas sensing materials.     

Efficient PKC inhibitor screening achieved using a quantitative CE‐LIF assay

An assay for protein kinase C delta (PKCδ) activity based on the quantification of a synthetic substrate using capillary electrophoresis with laser‐induced fluorescence detection was developed. The peptides labeled with fluorescein isothiocyanate F‐ERK (where ERK is extracellular signal‐regulated kinase) and the phosphorylated form, P‐F‐ERK, were utilized for the method development and validation. The migration time of F‐ERK and P‐F‐ERK were 6.3 ± 0.1 and 8.7 ± 0.2 min, respectively. LOD and LOQ values of F‐ERK were 2 and 6 ng/mL and those of P‐F‐ERK were 4 and 12 ng/mL. The correlation coefficients obtained from two standard curves were approximately 0.99. The reproducibility and accuracy of the method for F‐ERK ranged 1.5–4.7 and 86–109%, respectively, and those for P‐F‐ERK were 1.6–6.1 and 93–109%, respectively. The activity of PKCδ was studied in vitro using the human gastric cancer cell line MKN‐1. The use of PKCδ inhibitor candidates, including G?6983, bisindolylmaleimide II, staurosporine, and rottlerin in the assay resulted in IC₅₀ values of 50 nM, 15 nM, 795 nM, and 4 μM, respectively. Comparison of our assay with a commercial PKC kit revealed that our assay is more adaptable to differing enzyme isoforms. This method has potential for high throughput screening for kinase inhibitors as part of a drug discovery program.     

A new anti-inflammatory β-carboline alkaloid from the hairy-root cultures of Eurycoma longifolia

One new β-carboline alkaloid 7-methoxy-(9H-β-carbolin-1-il)-(E)-1-propenoic acid (1) together with 9-methoxycanthin-6-one (2) and 9-hydroxycanthin-6-one (3) were isolated from the hairy-root cultures of Eurycoma longifolia. The effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells were investigated. Compound 1 strongly inhibited the production of NO while 2 and 3 having weak or inactive effect. Consistently, compound 1 decreased the expression of cyclooxygenase-2 and inducible nitric oxide synthase.     

Sensitive detection of potassium ion using Prussian blue nanotube sensor

A model K⁺ sensor using Prussian blue nanotubes is fabricated by electrochemical deposition of Prussian blue (PB) within the nanochannels of a porous metal-coated membrane with partially covered pore openings. The PB nanotube sensor exhibits excellent stability giving reproducible peak potentials up to 500 measurement cycles, a very low detection limit of 2.0 × 10⁻⁸ M and extremely wide logarithmic linear ranges between 5.0 × 10⁻⁸–7.0 × 10⁻⁴ M and 7.0 × 10⁻⁴–1.0 M. Negligible interferences by Na⁺, Mg²⁺ and Ca²⁺ are observed and a rapid analysis time of 30 s is readily achieved. The ease of electrodeposition, high stability of PB nanotubes and outstanding analytical performance which surpasses conventional PB voltammetric and potentiometric sensors demonstrates potential sensing applications including ion sensors and biosensors using PB and other metal hexacyanoferrate nanotubes.     

Transient Absorption Dynamics and Nonlinear Optical Response in Colloidal Ag2S Quantum Dots

Optics and Spectroscopy - The mechanism of the nonlinear optical response of colloidal solutions of Ag2S quantum dots passivated with thioglycolic acid molecules is considered. Appearance of...     

Efficient and selective multicomponent oxidative coupling of two different aliphatic primary amines into thioamides by elemental sulfur

An efficient and selective multicomponent oxidative coupling of two different aliphatic primary amines into thioamides by elemental sulfur under solvent-free conditions has been developed.