葛根素与乙酰胆碱酯酶作用的分子动力学模拟

旨在阐明葛根素与乙酰胆碱酯酶(AChE)的分子作用机制,并为基于葛根素的类似物的AChE抑制剂的研发提供参考.运用AutoDock 4.2进行葛根素与AChE的分子对接,采用YASARA进行分子动力学模拟,利用MMPBSA.py模块计算复合体系的结合自由能,分析氨基酸的能量贡献.结果显示,葛根素与AChE对接体系含有4个氢键,2个π-π键. 5 ns后,体系均方根偏差(RMSD)趋于平衡,体系结合自由能为-18.19 kcal/mol.促体系结合的主要作用力是范德华力、静电作用力,非溶剂化能是主要的结合阻力.能量贡献最大的残基依次为Asn533、Lys530、Ala534、Pro529.这些研究为新型抑制剂的研发提供理论参考.     

反相高效液相色谱法测定小鼠脑中的梓醇

建立了小鼠脑组织中梓醇的反相高效液相色谱检测方法.色谱柱为Agilent Zorbax SB-AqC18亲水色谱柱,流动相为水-乙腈(99.5:0.5,V/V).流速为1.0mL/min,检测波长为210nm,柱温为30℃.梓醇含量在0.8-40.8μg/mL范围内线性关系良好,相关系数r为0.9999.平均回收率为70.0％-77.4％,RSD≤5.9％.按照5mg/kg给药剂量,C57小鼠腹腔注射梓醇,结果显示2h后,0.29％的给药量可以通过血脑屏障进入脑组织.所建立的RP-HPLC法简便,快速,准确,可靠,能较好的应用于小鼠脑组织中梓醇的测定.     

基于密度泛函方法的梓醇红外光谱的预测

梓醇是一种具有特殊药理活性的环烯醚萜苷类化合物。采用密度泛函(DFT)B3LYP/6-311G**方法对梓醇分子的几何构型进行全优化,得到其几何构型参数,进一步计算得到梓醇的红外振动光谱,振动频率校正因子为0.96。对计算得到的振动频率进行归属和解析并与实验测定得到的梓醇IR光谱特征峰比较,发现理论计算出的IR光谱与实验测定IR特征峰位具有很好的一致性,说明所采用的DFT方法能够用于梓醇分子几何构型的优化,预测难以得到标准对照品的环烯醚萜苷类化合物的IR光谱数据。     

乙酰胆碱酯酶抑制剂多奈哌齐衍生物的理性设计

阿尔茨海默症是老年人群中常见的慢性神经退行性疾病,严重损害老年人健康与生活质量.目前临床常使用乙酰胆碱酯酶抑制剂多奈哌齐等作为治疗药物.本文通过分子模拟方法研究了多奈哌齐和乙酰胆碱酯酶的作用模式;基于研究结果,对多奈哌齐衍生物进行理性设计,获得了化合物1.分子对接及药代动力学性质预测结果显示,化合物1具有和多奈哌齐相似的作用模式和成药性质.同时,分子静电势表面分布结果显示,甲基的引入可增强化合物1与关键氨基酸残基F295之间的氢键相互作用,可能具有较多奈哌齐更理想的活性.此外,化合物1能制备得到稳定的光学纯异构体;有利于减少临床上药物的使用量,降低副作用发生几率,具有进一步研究的价值.     

分子动力学模拟和自由能计算研究孕酮和孕酮受体蛋白的结合模式

孕酮在确立和维持妊娠中起到了关键的作用. 为了研究孕酮和孕酮受体蛋白的结合模式,进行了3.5纳秒的分子动力学模拟,用 MM-PBSA\GBSA方法计算了结合自由能. 自由能分解和丙氨酸扫描两种方法说明,残基 Leu718, Met756, Met759, Phe778 和 Tyr890 对于结合抑制剂作用明显,这些残基的主要作用能是范德瓦尔斯作用能. 这一研究结果可以指导孕酮受体蛋白抑制剂的优化     

生地黄的质量控制方法

建立中药材生地的质量控制方法.首先以正交试验来优化生地的提取工艺,然后以RPHPLC法测定生地中梓醇的含量.色谱条件如下,DiamonsilTM C18(200mm×4.6mm,5mm),柱温:30℃,流动相为水-乙腈(体积比99∶1),流速0.70mL·min-1,检测波长210nm.梓醇的质量浓度在0.0202-0.2020mg·mL-1(r=0.9999)与峰面积呈良好的线性关系,平均回收率为100.0％ (RSD=1.0％,n=9).本方法简便、准确,可用于生地药材的质量控制.     

分子动力学研究抑制剂APV与HIV-1蛋白酶的作用机制

采用分子动力学模拟和结合自由能计算研究了抑制剂APV与HIV-1蛋白酶的作用机制. 研究结果表明范德瓦尔斯作用主控了APV与HIV-1蛋白酶的结合. 采用基于残基的自由能分解方法计算了抑制剂-残基相互作用,结果表明9个残基Gly27、Ile32、Val47、Ile50、Ile84、Ala28′、Gly49′、Ile50′和Arg87′与APV产生了大于1.0 kcal/mol的强相互作用,而且证明CH-π,CH-O相互作用和极性作用是其结合的主要形式. 期待该结果可以为以HIV-1蛋白酶为靶标的抗艾滋病药物设计提供理论上的指导.     

分子动力学研究抑制剂APV与HIV-1蛋白酶的作用机制

采用分子动力学模拟和结合自由能计算研究了抑制剂APV与HIV-1蛋白酶的作用机制. 研究结果表明范德瓦尔斯作用主控了APV与HIV-1蛋白酶的结合. 采用基于残基的自由能分解方法计算了抑制剂-残基相互作用,结果表明9个残基Gly27、Ile32、Val47、Ile50、Ile84、Ala28′、Gly49′、Ile50′和Arg87′与APV产生了大于1.0 kcal/mol的强相互作用,而且证明CH-π,CH-O相互作用和极性作用是其结合的主要形式. 期待该结果可以为以HIV-1蛋白酶为靶标的抗艾滋病药物设计提供理论上的指导.     

分子动力学研究抑制剂APV与HIV-1蛋白酶的作用机制

采用分子动力学模拟和结合自由能计算研究了抑制剂APV与HIV-1蛋白酶的作用机制.研究结果表明范德瓦尔斯作用主控了APV与HIV-1蛋白酶的结合.采用基于残基的自由能分解方法计算了抑制剂-残基相互作用,结果表明9个残基Gly27、Ile32、Val47、Ile50、Ile84、Ala28'、Gly49'、Ile50'和Arg87'与APV产生了大于1.0 kcal/mol的强相互作用,而且证明CH-π,CH-O相互作用和极性作用是其结合的主要形式.期待该结果可以为以HIV-1蛋白酶为靶标的抗艾滋病药物设计提供理论上的指导.     

MDM2与抑制剂PDIQ作用机制的结合自由能计算研究

近年来p53-MDM2相互作用已成为抗癌药物设计的重要靶标.本工作采用分子动力学模拟和结合自由能计算研究抑制剂PDIQ与MDM2的结合模式.结果显示范德瓦尔斯作用是抑制剂结合的主体力量.基于残基的自由能分解计算结果表明CH-CH,CH-π和π-π相互作用驱动了抑制剂与MDM2的结合.这一研究可为抗癌药物的设计提供一定的理论指导.     

Sequential Cavity Method for Computing Free Energy and?Surface Pressure

We propose a new method for the problems of computing free energy and surface pressure for various statistical mechanics models on a lattice ℤ ^d . Our method is based on representing the free energy and surface pressure in terms of certain marginal probabilities in a suitably modified sublattice of ℤ ^d . Then recent deterministic algorithms for computing marginal probabilities are used to obtain numerical estimates of the quantities of interest. The method works under the assumption of Strong Spatial Mixing (SSP), which is a form of a correlation decay. We illustrate our method on the hard-core and monomer-dimer models, on which we improve several earlier estimates. For example we show that the exponential of the monomer-dimer coverings of ℤ³ belongs to the interval [0.78595,0.78599], improving best previously known estimate of [0.7850,0.7862] obtained in (Friedland and Peled in Adv. Appl. Math. 34:486–522, 2005; Friedland et al. in J. Stat. Phys., 2009). Moreover, we show that given a target additive error ε>0, the computational effort of our method for these two models is (1/ε) ^O(1) both for the free energy and surface pressure values. In contrast, prior methods, such as the transfer matrix method, require exp ((1/ε) ^O(1)) computation effort.     

Interaction Between Isoquercitrin and Bovine Serum Albumin by a Multispectroscopic Method

ABSTRACT

The interaction of isoquercitrin and bovine serum albumin (BSA) was investigated by means of fluorescence spectroscopy (FS), resonance light scattering spectroscopy (RLS), and ultraviolet spectroscopy (UV). The apparent binding constants (K _a) between isoquercitrin and BSA were 5.37 × 10⁵ L mol^?1 (293.15 K) and 2.34 × 10⁵ L mol^?1 (303.15 K), and the binding site values (n) were 1.18 ± 0.03. According to the Förster theory of non-radiation energy transfer, the binding distances (r) between isoquercitrin and BSA were 1.94 and 1.95 nm at 293.15 K and 303.15 K, respectively. The experimental results showed that the isoquercitrin could be inserted into the BSA, quenching the inner fluorescence by forming the isoquercitrin–BSA complex. The addition of increasing isoquercitrin to BSA solution leads to the gradual enhancement in RLS intensity, exhibiting the formation of the aggregate in solution. It was found that both static quenching and non-radiation energy transfer were the main reasons for the fluorescence quenching. The entropy change and enthalpy change were negative, which indicated that the interaction of isoquercitrin and BSA was driven mainly by van der Waals interactions and hydrogen bonds. The process of binding was a spontaneous process in which Gibbs free energy change was negative.     

Consequences of the center–of–mass correction in nuclear mean–field models

We study the influence of the scheme for the correction for spurious center–of–mass motion on the fit of effective interactions for self–consistent nuclear mean–field calculations. We find that interactions with very simple center–of–mass correction have significantly larger surface coefficients than interactions for which the center–of–mass correction was calculated for the actual many–body state during the fit. The reason for that is that the effective interaction has to counteract the wrong trends with nucleon number of all simplified schemes for center–of–mass correction which puts a wrong trend with mass number into the effective interaction itself. The effect becomes clearly visible when looking at the deformation energy of largely deformed systems, e.g. superdeformed states or fission barriers of heavy nuclei. Received: 6 September 1999     

局部热力学平衡状态下的等离子体电导率计算

在ZollwegLiebermann模型(ZL模型)的基础上,结合高温条件下的量子机理作用,考虑了电子与中性粒子的碰撞关系,最终得出修正后的电导率模型,并对局部热力学平衡状态下的水中放电等离子体的粒子数密度及电导率进行了模拟计算.计算结果表明压力为定值的情况下,水中放电等离子体的总粒子数密度随温度变化呈下降趋势,温度达到15000 K时,一次电离达最大值.电导率随温度增加总体呈上升趋势,温度低于12000 K时,电子与中性粒子的碰撞起主导作用,而温度高于25000 K时,电子与离子的碰撞起主导作用.     

Interaction of Sulfadiazine with Model Water Soluble Proteins: A Combined Fluorescence Spectroscopic and Molecular Modeling Approach

The binding behavior of antibacterial drug sulfadiazine (SDZ) with water soluble globular proteins like bovine as well as human serum albumin (BSA and HSA, respectively) and lysozyme (LYS) was monitored by fluorescence titration and molecular docking calculations. The experimental data reveal that the quenching of the intrinsic protein fluorescence in presence of SDZ is due to the strong interaction in the drug binding site of the respective proteins. The Stern-Volmer plot shows positive deviation at higher quencher concentration for all the proteins and was explained in terms of a sphere of action model. The calculated fluorophore-quencher distances vary within 4?~?11 Å in different cases. Fluorescence experiments at different temperature indicate thermodynamically favorable binding of SDZ with the proteins with apparently strong association constant (~10⁴–10⁵ M^?1) and negative free energy of interaction within the range of ?26.0?~??36.8 kJ mol^?1. The experimental findings are in good agreement with the respective parameters obtained from best energy ranked molecular docking calculation results of SDZ with all the three proteins.     

局部热力学平衡状态下的等离子体电导率计算

在Zollweg & Liebermann模型（Z&L模型）的基础上,结合高温条件下的量子机理作用,考虑了电子与中性粒子的碰撞关系,最终得出修正后的电导率模型,并对局部热力学平衡状态下的水中放电等离子体的粒子数密度及电导率进行了模拟计算.计算结果表明压力为定值的情况下,水中放电等离子体的总粒子数密度随温度变化呈下降趋势,温度达到15000 K时,一次电离达最大值.电导率随温度增加总体呈上升趋势,温度低于12000 K时,电子与中性粒子的碰撞起主导作用,而温度高于25000 K时,电子与离子的碰撞起主导作用.     

The structure of the distortion free-energy density in nematics: Second-order elasticity and surface terms

Summary By means of a phenomenological approach, we demonstrate that the mixed splay-bend elastic constantK ₁₃ in the free energy density of nematic liquid crystals must be considered zero, unless the bulk contributions of the squares of the distortion second-order derivatives are taken into account, together with the squares of the first-order derivatives times the second-order derivatives, and with the fourth powers of the first-order derivatives. Such contributions just reduce to one in the presence of—and close to—a threshold. Furthermore, the saddle-splayK ₂₄-term instead is shown always to play an essential role, as the bulk first-order elasticity, in determining the distortion free energy of nematics with weak anchoring subjected to spatial deformations. Finally, the new surfacelike elastic constants are shown to have a nilpotent character: thus they behave as well asK ₂₄ from the point of view of the variational calculus. Work presented at the second USSR-Italy Bilateral Meeting on Liquid Crystals held in Moscow, September 15–21, 1988.     

The Interaction of a New Schiff Base Ligand with Human Serum Albumin: Molecular Docking and Molecular Dynamics Simulation Studies

The interaction of a new heterocyclic Schiff base bearing pyridine and pyrimidine cycles, with human serum albumin (HSA) using molecular docking and molecular dynamics simulation methods was examined. Molecular docking studies showed that the ligand was bonded to the IB domain of the protein. It was found that there was one hydrogen bond interaction between HSA and the ligand. The standard Gibbs free energy for binding of the ligand to HSA was calculated as ?9.63 kcal.mol^?1. The results of the molecular dynamics simulation showed that the root mean square deviation (RMSD) of the non-liganded HSA and the HSA–ligand complex reached equilibration after 1000 ps. The study of the radius of gyration revealed that there was a conformational change when the HSA–ligand complex was formed. Finally, analyzing the RMS fluctuations (RMSF) suggested that the structure of the ligand binding site remained approximately rigid during the simulation.     

Fine structure of the dipole excitations of the even-even 160Gd nucleus in the spectroscopic region

In this study, the result of calculations using rotational, translational and Galilean invariant quasiparticle random-phase approximation is presented for the low-lying dipole excitations in the even-even ¹⁶⁰Gd nucleus. Calculations are carried out for both ΔK=1 and ΔK=0 branches. The analysis shows that the main part of spin-1 states, observed at energy 2.4–4 MeV in ¹⁶⁰Gd, have M1 character and are interpreted as main fragments of the scissors mode. The calculations indicate the presence of a few prominent negativeparity dipole ΔK=1 states in the investigated energy region, in agreement with experiment.      

Influence of surface topography and annealing temperature on the surface and volume of dissipation electrical energy and Spitzer–Fan model in Al doped ZnO films

The aim of this work is to investigate the optical constants of aluminum doped zinc oxide films annealed at different temperatures. With increasing temperature, due to decreasing unfilled inter-granular volume per unit thickness, the optical transmittance spectra of films were increased. The films have a normal dispersion in the spectral range 400?<?λ?<?500 nm and the anomalous dispersion in IR range. The lattice dielectric constants ε_L, the free charge carriers concentration, the plasma frequency, Spitzer–Fan model and the waste of electrical energy as heat of films can be analyzed using the refractive index n and the extinction coefficient k spectra. With increasing annealing temperature, the lattice dielectric constants ε_L of films decrease however the free charge carriers concentration of films increase. The free carrier electric susceptibility of films annealed at 600 °C has maximum value. The energy loss by the free charge carriers when traversing the bulk and surface of films annealed at 600 °C has a minimum value in the near fundamental absorption edge and it with increasing energy increases.