Computational combinatorial ligand design: Application to human α-thrombin

Summary A new method is presented for computer-aided ligand design by combinatorial selection of fragments that bind favorably to a macromolecular target of known three-dimensional structure. Firstly, the multiple-copy simultaneous-search procedure (MCSS) is used to exhaustively search for optimal positions and orientations of functional groups on the surface of the macromolecule (enzyme or receptor fragment). The MCSS minima are then sorted according to an approximated binding free energy, whose solvation component is expressed as a sum of separate electrostatic and nonpolar contributions. The electrostatic solvation energy is calculated by the numerical solution of the linearized Poisson-Boltzmann equation, while the nonpolar contribution to the binding free energy is assumed to be proportional to the loss in solvent-accessible surface area. The program developed for computational combinatorial ligand design (CCLD) allows the fast and automatic generation of a multitude of highly diverse compounds, by connecting in a combinatorial fashion the functional groups in their minimized positions. The fragments are linked as two atoms may be either fused, or connected by a covalent bond or a small linker unit. To avoid the combinatorial explosion problem, pruning of the growing ligand is performed according to the average value of the approximated binding free energy of its fragments. The method is illustrated here by constructing candidate ligands for the active site of human -thrombin. The MCSS minima with favorable binding free energy reproduce the interaction patterns of known inhibitors. Starting from these fragments, CCLD generates a set of compounds that are closely related to high-affinity thrombin inhibitors. In addition, putative ligands with novel binding motifs are suggested. Probable implications of the MCSS-CCLD approach for the evolving scenario of drug discovery are discussed.     

HPLC separation of hydrogenated derivatives of buckminsterfullerene

Summary The effect of composition and flow rate of the mobile phase on the HPLC separation of hydrogenated buckminsterfullerene (C₆₀H_n n=2–38) was investigated on BuckySep column. Toluene was used as the basic solvent and hexane, heptane, cyclohexane, THF, acetonitrile, acetone, ethanol and 2-propanol as co-solvents. The fraction of co-solvents was varied 10–80%, and the flow rate 1–0.1 mL min⁻¹. Toluene-acetonitrile 65∶35 and toluene-acetone 50∶50 provided the best separation. Under the best conditions complete separation of C₆₀H₂ and almost complete separation of the four most abundant isomers of C₆₀H₄ were achieved. Separation of derivatives with higher hydrogen content was very poor. Presented at: Balaton Symposium on High-Performance Separation Methods, Siófok, Hungary, September 3–5, 1997     

Bauhinia forficata Link Infusions: Chemical and Bioactivity of Volatile and Non-Volatile Fractions

This study aimed to evaluate Bauhinia forficata infusions prepared using samples available in Rio de Janeiro, Brazil. As such, infusions at 5% (w/v) of different brands and batches commercialized in the city (CS1, CS2, CS3, and CS4) and samples of plant material botanically identified (BS) were evaluated to determine their total phenolic and flavonoid contents (TPC and TFC), antioxidant capacity (ABTS^•+, DPPH^•, and FRAP assays), phytochemical profile, volatile compounds, and inhibitory effects against the α-amylase enzyme. The results showed that infusions prepared using BS samples had lower TPC, TFC and antioxidant potential than the commercial samples (p < 0.05). The batch averages presented high standard deviations mainly for the commercial samples, corroborating sample heterogeneity. Sample volatile fractions were mainly composed of terpenes (40 compounds identified). In the non-volatile fraction, 20 compounds were identified, with emphasis on the CS3 sample, which comprised most of the compounds, mainly flavonoid derivatives. PCA analysis demonstrated more chemical diversity in non-volatile than volatile compounds. The samples also inhibited the α-amylase enzyme (IC₅₀ value: 0.235–0.801 mg RE/mL). Despite the differences observed in this work, B. forficata is recognized as a source of bioactive compounds that can increase the intake of antioxidant compounds by the population.     

基于镜像分析的空心导管光束整形原理研究

基于镜像原理,对空心导管LD面阵光束整形的原理和输出光场的特点进行了分析,并对LD面阵光束经过空心导管后的光强分布进行了仿真.发现空心导管将LD不同角度范围的光束进行分割,并在出射面内叠加的光束整形原理.通过仿真得出由于发散角较大以及各分割角度范围光束角度不连续,使出射面上的平顶光束发生畸变,只适于泵浦薄激光介质的结论.     

基于剪切修正GTN模型的金属弹性退化机理研究

许多金属材料在进行显微或宏观压入测试时,测得的弹性模量会随着压入深度的增大而不断降低.考虑到在压痕测试过程中金属材料并不产生明显的裂纹,这种性能退化应是由材料的损伤引起.然而,经典损伤理论认为以受压和受剪为主的压入变形不会引起材料软化和损伤.本文结合剪切变形下材料损伤的萌生和演化机理,对经典的GTN(Gurson-Tvergaard-Needleman)模型进行了修正,对压入测试进行了有限元模拟.模拟结果显示,材料在压入过程中的损伤是由现有空洞的扭曲变形和次级空洞的萌生共同引起,如果只考虑现有空洞变形则会低估材料在压入变形过程中的损伤演变.     

空间层叠矩形阵列式角多路解码光路设计

根据角多路技术原理,提出了一种矩形阵列空间层叠形式的解码光路结构和先分组解码再组内解码的两步解码方式,并针对本实验室的高功率准分子激光系统给出了具体的解码光路设计实例。该方法具有解码精度高,设计误差小,与光路准直、激光参数测量系统等兼容性好,便于加工制作和安装调试等优点。     

The DI-SPME Method for Determination of Selected Narcotics and Their Metabolites,and Application to Bone Marrow and Whole Blood Analysis

The present investigation utilised the quick and easy SPME/LC-MS method to determine selected narcotic substances and their metabolites in whole blood. The study included qualitative analysis and validation of the method. Analytes were determined in the linearity range of 25–300 ng/mL. The precision during and between days (in general CV < 13.41%), and the LOD which results in between 0.36 and 11.08 ng/mL, and the LOQ between 1.20 and 36.90 ng/mL were investigated. The validation results obtained, as well as the results of subsequent in-laboratory tests, confirmed the applicability of the method in the analysis of blood samples. An attempt to apply the method to the analysis of bone marrow samples has yielded promising results; however, more detailed studies are needed in this area.     

6σ管理和统计技术

从6σ名称,绿带、黑带的评定标准和培训内容都体现了统计技术是6σ管理的核心技术。DMAIC统计技术应用模式虽有不足,最大功绩是使应用统计技术简单化,实际应用者认识了统计技术的重要性。     

两粒子相容可观察量共同本征矢的推导

利用有序算符正规乘积内的积分技术(IWOP)和待定系数法,推导出了两粒子相对坐标算符x^1-x^2与总动量算符p^1 p^2的共同本征矢|η〉在Fock空间中的展开式,为解决这类问题提供了一种行之有效的方法,这对提高学生的学习素质和加深学生对理论知识的理解会有一定的帮助.     

双波长荧光法同时测定水溶解态的茚、萘和菲

建立了一种同时测定水体中多组分溶解态多环芳烃的新方法。为消除共存组分干扰,利用三维荧光谱确定茚、萘和菲的最佳测量点为A(λex250.0nm,λem308.0nm)、B(λex225.0nm,λem335.0nm)、C(λex250.0nm,λem364.0nm);萘和菲相应的最佳参比波长分别为292.5nm和286.7nm,所建方法用于水体中茚、萘和菲的同时测定。其线性范围分别为:2.00×10-7～2.00×10-5mol/L、5.00×10-8～3.50×10-6mol/L和1.00×10-8～1.00×10-6mol/L;检出限分别为:8.63×10-9、1.01×10-8和5.29×10-10mol/L;相对标准偏差分别为:1.1%、1.0%和0.7%(n=7)。方法用于自来水样和海水样的测定,结果满意。