Hydrogen‐bonding interactions in the active site of a low molecular weight protein‐tyrosine phosphatase

Molecular dynamics simulation of the Michaelis complex, phospho‐enzyme intermediate, and the wild‐type and C12S mutant have been carried out to examine hydrogen‐bonding interactions in the active site of the bovine low molecular weight protein‐tyrosine phosphatase (BPTP). It was found that the S_γ atom of the nucleophilic residue Cys‐12 is ideally located at a position opposite from the phenylphosphate dianion for an inline nucleophilic substitution reaction. In addition, electrostatic and hydrogen‐bonding interactions from the backbone amide groups of the phosphate‐binding loop strongly stabilize the thiolate anion, making Cys‐12 ionized in the active site. In the phospho‐enzyme intermediate, three water molecules are found to form strong hydrogen bonds with the phosphate group. In addition, another water molecule can be identified to form bridging hydrogen bonds between the phosphate group and Asp‐129, which may act as the nucleophile in the subsequent phosphate hydrolysis reaction, with Asp‐129 serving as a general base. The structural difference at the active site between the wild‐type and C12S mutant has been examined. It was found that the alkoxide anion is significantly shifted toward one side of the phosphate binding loop, away from the optimal position enjoyed by the thiolate anion of the wild‐type enzyme in an S_N2 process. This, coupled with the high pK_a value of an alcoholic residue, makes the C12S mutant catalytically inactive. These molecular dynamics simulations provided details of hydrogen bonding interactions in the active site of BPTP, and a structural basis for further studies using combined quantum mechanical and molecular mechanical potential to model the entire dephosphorylation reaction by BPTP. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1192–1203, 2000     

Anti-Hyperglycemic Effects of Refined Fractions from Cyclocarya paliurus Leaves on Streptozotocin-Induced Diabetic Mice

To identify the chemical components responsible for the anti-hyperglycemic effect of Cyclocarya paliurus (Batal.) Iljinsk (Juglandaceae) leaves, an ethanol extract (CPE) and a water extract (CPW) of C. paliurus leaves, as well as their total flavonoids (CPF), triterpenoids (CPT) and crude polysaccharides (CPP), were prepared and assessed on streptozotocin (STZ)-induced diabetic mice. After being orally administrated once a day for 24 days, CPF (300 mg/kg), CPP (180 mg/kg), or CPF+CPP (300 mg/kg CPF + 180 mg/kg CPP) treatment reversed STZ-induced body weight and muscle mass losses. The glucose tolerance tests and insulin tolerance tests suggested that CPF, CPP, and CPF+CPP showed anti-hyperglycemic effect in STZ-induced diabetic mice. Furthermore, CPF enhances glucose-stimulated insulin secretion in MIN6 cells and insulin-stimulated glucose uptake in C2C12 myotubes. CPF and CPP suppressed inflammatory cytokine levels in STZ-induced diabetic mice. Additionally, CPF and CPP improved STZ-induced diabetic nephropathy assessed by H&E staining, blood urea nitrogen content, and urine creatinine level. The molecular networking and Emperor analysis results indicated that CPF showed potential anti-hyperglycemic effects, and HPLC–MS/MS analysis indicated that CPF contains 3 phenolic acids and 9 flavonoids. In contrast, CPT (650 mg/kg) and CPC (300 mg/kg CPF + 180 mg/kg CPP + 650 mg/kg CPT) did not show anti-hyperglycemic effect. Taken together, polysaccharides and flavonoids are responsible for the anti-hyperglycemic effect of C. paliurus leaves, and the clinical application of C. paliurus need to be refined.     

A molecular mechanics force field for NAD+ NADH,and the pyrophosphate groups of nucleotides

Empirical force field parameters for nicotinamide (NIC⁺) and 1,4-dihydronicotinamide (NICH) were developed for use in modeling of the coenzymes nicotinamide adenine dinucleotide (NAD⁺) and NAD hydride (NADH). The parametrization follows the methodology used in the development of the CHARMM22 all-hydrogen parameters for proteins, nucleic acids, and lipids. Parametrization of inorganic phosphate for use in adenosine di- and triphosphates (e.g., ADP and ATP) is also presented. While high level ab initio data, such as conformational energies, dipole moments, interactions with water, and vibrational frequencies, were adequately reproduced by the developed parameters, strong emphasis was placed on the successful reproduction of experimental geometries and crystal data. Results for molecular dynamics crystal simulations were in good agreement with available crystallographic data. Simulations of NAD⁺ in the enzyme alcohol dehydrogenase compared quite favorably with experimental geometries and protein matrix interactions. © 1997 by John Wiley & Sons, Inc.     

Polarimetric-Spectral-Sensitive Compressed Ultrafast Photography Enables Real-Time Intensity Visualization of Time-Varying Polarized Ultrafast Laser Pulses

Ultrafast laser pulses with complex spatiotemporal and polarization couplings have shown great application prospects in coherent control, particle acceleration, molecular dynamics excitation, and chiral or anisotropic detection. It is very important to observe the polarization-coupled ultrafast laser pulses for characterizing the performance of laser source and understanding the laser-matter interaction, but there is currently no detection technique that can completely characterize them, including the spatio-, spectral-, and polarimetric-temporal information. In this work, a polarimetric-spectral-sensitive has been compressed ultrafast photography (PS-CUP) to realize the real-time intensity visualization of time-varying polarized (TP) ultrafast laser pulses. PS-CUP can not only distinguish the polarization state of a TP pulse, but also realize the spatio-, spectral- and polarimetric-temporal measurement. To demonstrate the ability of polarization resolving detection, PS-CUP is used to successfully distinguish between the sinistral and dextral TP pulses and measure the angle and degree of linear polarization of a dextral TP pulse, respectively, and the experimental results are highly consistent with theoretical simulations. Owing to the unprecedented multidimensional detection ability, PS-CUP is prospected to provide a powerful tool for the diagnosis of various complex ultrafast laser pulses and the detection of ultrafast chiral optics.     

固体核磁共振定量表征方法及其在高分子结构研究中的应用

高分子材料拥有众多优良的特性,使其广泛应用于现代社会的生产、生活及高新科技等领域。对于高分子特性的研究离不开微观物理、化学结构的定量表征。在众多表征高分子结构定量信息的实验技术中,固体核磁共振（SSNMR）发挥着重要的作用。它可以定量表征高分子的化学结构、材料体系的相成分及共混组分等,从而实现了难溶高分子产物的结构鉴定,以及高分子微观物理、化学结构关联材料性能的研究。然而,传统的SSNMR定量方法（直接激发法,DD）往往需要耗费十几个小时甚至数天的实验时间。交叉极化方法（CP）虽然大大缩短了实验时间,却往往无法提供定量的信息。基于此,研究者们提出了多个定量CP的实验方法,同时满足了方法定量性和实验耗时短的需求。本文综述了传统SSNMR定量方法及几种定量的CP方法,简单介绍了每个方法的基本原理,并平行阐述了实验方法的应用范围及特点,通过部分实例展示了SSNMR定量方法在高分子材料领域的应用价值,为研究者研发新型的高分子材料提供可靠并有效的结构表征手段。     

THE SHEAR LAG EFFECT OF BOX BEAMS WITH VARYING LATERAL LOADING LOCATIONS 1)

对箱梁各翼板(顶板、悬臂板、底板)分设不同剪力滞广义纵向位移,其横向分布均取二次抛物线形式,并引入载荷横向位置参数η,以分析载荷横向变位对剪力滞效应的影响.运用能量变分原理,建立剪力滞控制微分方程,求解了简支梁和悬臂梁在均布载荷作用下的控制微分方程的解.算例分析表明:载荷横向变位改变直接承受载荷的翼板的正负剪力滞特性,对非直接承载翼板只改变其应力幅度;箱梁横向框架效应对直接承载翼板纵向应力的贡献远远大于剪切变形.与块体有限元分析结果较吻合,表明该算法能较准确分析载荷横向变位作用下箱梁剪力滞的变化规律.     

用离子色谱法测定水中的二氧化氯、氯、亚氯酸根及氯酸根

建立了一种测定水中的ClO2、Cl2、ClO2^-、ClO3^-离子色谱法,在含有碳酸氢钠缓冲溶液的中性条件下,用NaNO2将ClO2、Cl2还原为ClO2^-、Cl^-,通过测定ClO^-和NO3^-的变化值,间接测定ClO2和Cl2。加入硫代乙酰胺(TAA)作掩蔽剂测定ClO2^-。     

多线性分数次积分算子交换子的有界性

本文利用sharp极大函数的估计,证明了一类由多线性分数次积分算子和BMO(Rn)函数生成的交换子的Lp(Rn)有界性.     

不可压缩流的并行两水平稳定有限元算法

提出一种数值求解定常不可压缩Stokes方程的并行两水平Grad-div稳定有限元算法。首先在粗网格中求解Grad-div稳定化的全局解, 再在相互重叠的细网格子区域上并行纠正。通过对稳定化参数、粗细网格尺寸恰当的选取, 该方法可得到最优收敛率, 数值结果验证了算法的高效性。     

金纳米颗粒等离子体共振吸收光谱检测头孢唑啉

根据金纳米粒子等离子体共振吸收引起的溶液颜色变化,建立了一种快速、简便检测头孢唑啉的色度分析方法.方法线性范围为0.1～5.0 μmol/L,检测限为14 nmol/L.将该方法用于头孢唑啉钠粉针剂的分析,回收率在97.4％～100.2％之间,相对标准偏差小于6.1％.