Multiple ligand simultaneous docking: Orchestrated dancing of ligands in binding sites of protein

Present docking methodologies simulate only one single ligand at a time during docking process. In reality, the molecular recognition process always involves multiple molecular species. Typical protein–ligand interactions are, for example, substrate and cofactor in catalytic cycle; metal ion coordination together with ligand(s); and ligand binding with water molecules. To simulate the real molecular binding processes, we propose a novel multiple ligand simultaneous docking (MLSD) strategy, which can deal with all the above processes, vastly improving docking sampling and binding free energy scoring. The work also compares two search strategies: Lamarckian genetic algorithm and particle swarm optimization, which have respective advantages depending on the specific systems. The methodology proves robust through systematic testing against several diverse model systems: E. coli purine nucleoside phosphorylase (PNP) complex with two substrates, SHP2NSH2 complex with two peptides and Bcl‐xL complex with ABT‐737 fragments. In all cases, the final correct docking poses and relative binding free energies were obtained. In PNP case, the simulations also capture the binding intermediates and reveal the binding dynamics during the recognition processes, which are consistent with the proposed enzymatic mechanism. In the other two cases, conventional single‐ligand docking fails due to energetic and dynamic coupling among ligands, whereas MLSD results in the correct binding modes. These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X‐ray crystallographic maps, and aiding fragment‐based drug design, respectively. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

两端叠层结构的中长波量子阱红外探测器

采用分子束外延技术生长了两个叠层结构的双色量子阱红外探测器结构,并经过光刻和湿法刻蚀制作成两端结构的量子阱红外探测器单元器件. 通过改变量子阱势垒高度,势阱宽度,掺杂浓度,重复周期数等器件参数,可以使总电压在两个叠层之间产生适当的分布,从而使器件表现出不同的电压响应特点. 光电流谱测量显示,器件1随着外加偏置电压可实现对于中波大气红外窗口(3—5 μm)和长波大气红外窗口(8—12 μm)红外响应的切换,器件2在不同的偏置电压下可以对这两个波段同时做出响应. 本文探讨了两端叠层结构量子阱红外探测器的工作原 关键词： 电压调制 同时响应 量子阱红外探测器 双波段     

APPROXIMATION BY COMPLEX SZASZ-DURRMEYER OPERATORS IN COMPACT DISKS

In the present paper, we deal with the complex Szasz-Durrmeyer operators and study Voronovskaja type results with quantitative estimates for these operators attached to analytic functions of exponential growth on compact disks. Also, the exact order of approximation is found.     

A Notion of Nonlocal Curvature

We consider a nonlocal (or fractional) curvature and we investigate similarities and differences with respect to the classical local case. In particular, we show that the nonlocal mean curvature can be seen as an average of suitable nonlocal directional curvatures and there is a natural asymptotic convergence to the classical case. Nevertheless, different from the classical cases, minimal and maximal nonlocal directional curvatures are not in general attained at perpendicular directions and, in fact, one can arbitrarily prescribe the set of extremal directions for nonlocal directional curvatures. Also the classical directional curvatures naturally enjoy some linear properties that are lost in the nonlocal framework. In this sense, nonlocal directional curvatures are somewhat intrinsically nonlinear.     

多参数二次特征值问题重特征值的灵敏度分析

本文研究解析依赖于多参数的二次特征值问题重特征值的灵敏度分析,得到了重特征值的方向导数,证明了相应的特征向量矩阵和特征值平均值的解析性,给出了其一阶偏导数的表达式．然后以这些结论为基础,定义了二次特征值问题重特征值及其不变子空间的灵敏度,并给出了确定二次特征值问题所含矩阵中敏感元素的方法．     

Transformation of the spectrum of the longitudinal modes of a semiconductor laser on introduction of its radiation into fiber light guides

We investigated the influence exerted by the radius of the bend of fiber light guides with light-transmitting cores of different diameters on the transformation of the spectrum of longitudinal modes of the semiconductor laser radiation introduced into them. It is shown that the bended segment of the light guide acts as a spectrum selector, and the spectral composition of the radiation at the output of a light guide is different in different spots of the speckle structure. Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 67, No. 2, pp. 260–263, March–April, 2000.     

五像限法太阳自动跟踪仪

介绍由两心圆组成的等面积五像限光测量装置工作原理，即当光线与光电池垂直时其投影光斑经过一透镜后正好安全覆盖五片光电池，当光线与光电池成一夹角时，其投影光斑必然发生偏移，将光主在光电池上的偏移转移成光电流差值的变化，实现装置自动跟踪太阳。     

Simultaneous quantification of curcuminoids and xanthorrhizol in Curcuma xanthorrhiza by high-performance liquid chromatography

A new method for simultaneous quantification of curcuminoids and xanthorrhizol (XNT) in Curcuma xanthorrhiza was developed and validated using high-performance liquid chromatography with diode-array UV–Vis detector. The chromatographic separation was achieved on a Phenomenex C18 at room temperature with the mobile-phase acetonitrile ?0.001% formic acid in gradient elution system and delivered at a flow rate of 1?mL/min. Detection wavelength 425?nm was used for curcuminoids and 224?nm for XNT. System suitability, linearity, precision, accuracy, limit of detection, limit of quantitation, and stability were evaluated and were found in good agreement with Association of Official Analytical Chemists guidelines for single-laboratory validation. The proposed method was found to be precise, accurate, and reliable and also could be applied for the simultaneous quantitative analysis of curcuminoids and XNT in C. xanthorriza raw material and its herbal medicinal product.     

Simultaneous determination of phthalates and adipates in human serum using gas chromatography–mass spectrometry with solid‐phase extraction

A gas chromatography–mass spectrometry assay was developed and validated for the simultaneous determination of phthalates and adipates in human serum. The phthalates and adipates studied were dimethyl phthalate, diethyl phthalate, dibutyl phthalate, benzylbutyl phthalate, di‐2‐ethylhexyl phthalate, di‐n‐octyl phthalate, diethyl adipate, dibutyl adipate, diisobutyl adipate, bis(2‐butoxyethyl) adipate and di‐2‐ethylhexyl adipate, with diisooctyl phthalate as internal standard. The extraction and cleaning up procedure was carried out with solid‐phase extraction cartridges containing dimethyl butylamine groups, which showed extraction efficiencies over 88% for each analyte and the internal standard. The calibration curves obtained were linear with correlation coefficients greater than 0.98. For all analytes, the assay gave CV% values for intra‐day precision from 4.9 to 13.3% and mean accuracy values from 91.4 to 108.4%, while inter‐day precision was 5.2–13.4% and mean accuracy 91.0–110.2%. The limits of detection for the assay of phthalates and adipates were in the range 0.7–4.5 ng/mL. The method is simple, sensitive and accurate, and allows for simultaneous determination of nanogram levels of phthalates and adipates in human serum. It was successfully applied to an investigation on the level of phthalates and adipates in a non‐occupationally exposed population.