Crystallization and Preliminary Crystallographic Studies of Cucurmosin 2,a Ribosome-inactivating Protein from the Sarcocarp of Cucurbita moschata

Cucurmosin 2, a type 1 ribosome-inactivating protein （RIP） isolated from sarcocarp of Cucurbita moschata, has been crystallized by the vapor-diffusion method using PEG6000 as the precipitant. The crystals belong to the orthorhombic space group P212121, with unit cell parameters a = 55.853, b = 65.507, c = 91.754 А, and have one molecule per asymmetric unit. X-ray data have been collected to 1.8А, using a synchrotron source.     

Structure-Based Discovery of ABCG2 Inhibitors: A Homology Protein-Based Pharmacophore Modeling and Molecular Docking Approach

ABCG2 is an ABC membrane protein reverse transport pump, which removes toxic substances such as medicines out of cells. As a result, drug bioavailability is an unexpected change and negatively influences the ADMET (absorption, distribution, metabolism, excretion, and toxicity), leading to multi-drug resistance (MDR). Currently, in spite of promising studies, screening for ABCG2 inhibitors showed modest results. The aim of this study was to search for small molecules that could inhibit the ABCG2 pump. We first used the WISS MODEL automatic server to build up ABCG2 homology protein from 655 amino acids. Pharmacophore models, which were con-structed based on strong ABCG2 inhibitors (IC₅₀ < 1 μM), consist of two hydrophobic (Hyd) groups, two hydrogen bonding acceptors (Acc2), and an aromatic or conjugated ring (Aro|PiR). Using molecular docking method, 714 substances from the DrugBank and 837 substances from the TCM with potential to inhibit the ABCG2 were obtained. These chemicals maybe favor synthesized or extracted and bioactivity testing.     

雪卡毒素毒性机理的分子对接及分子动力学研究

采用分子对接和分子动力学方法,研究了雪卡毒素与其毒性作用靶点之一钠通道的结合模式,并与钠通道阻滞剂奎尼丁比较.研究结果表明,雪卡毒素、奎尼丁与钠通道作用方式有所不同.分子动力学模拟表明,对接受体-配体复合物体系在2.5 ns的模拟过程中稳定.奎尼丁在钠通道中央与GLU1784,THR1858各形成1个稳定氢键,吡啶环与...     

NMR和分子力学法研究溶液中有机分子结构

在分子力学能量优化项中加入由ＮＭＲ实验得到的几何参数二面角（相应于~３Ｊ_（ＨＨ）耦合常数）及质子间距所构造的约束函数，使分子力学计算得到的能量极小点的分子构象，其耦合常数（~３Ｊ_（ＨＨ））及质子间距同ＮＭＲ实验结果相符合。文中以（±）－３－（４＇－甲苯基）－１－氮杂双环［２．２．２］－３－辛醇为例，采用自编的ＮＭＲ参数约束的分子力学计算程序ＭＭ２ＮＪ对其构象进行了计算。所得结果与Ｘ射线衍射法比较，有较好的一致性     

Crystal Structure of Crotin Ⅱ at 2.5  Resolution

1INTRODUCTIONTheplanttoxin,CrotinIisoneoftheribosomeinactivatingproteins(RIPs)[l3.AccordingtothemolecularmechanismofactiontheRIPscanbedividedintotwokinds[2:.OnebelongstoRNAN-glycosidasewhichisclassifiedastwotypes.TypeIconsistsofasinglepolypeptidechain,forexample,trichosanthinandsaporin-Typellconsistsoftwochains,suchasricinandabrin'ThiskindofRIPshydrolysesasingleN-glycosidicbondbetweenanadenineandriboseatspecificnu-cleotide(A4324)of28SrRNAintheribosomes[3i.ThesecondkindofRIPsbel…     

平面环辛四烯:分子结构操纵实例

环辛四烯为一不平面分子,一般相信,理论中的平面环辛四烯需要将一对不成对电子填入两个简并不成键轨道,因而引起之伪扬-泰勒效应,可使带 D_(8h)对称性之平面环辛四烯非平面化而成“船”形的结构。本文简单介绍加减电子法、带张力环稠合法、键长缩短法和金属螫合法四种可使不平面之环辛四烯成为平面方法。然而,随有机合成方法之不断进展,在将来可能出现更多改变环辛四烯不平面结构的方法。我们在此文章提出化合物98即为一个可使环辛四烯成为平面的例子。98之合成将成为有机合成化学家的一个新的挑战。     

银团簇结构与特性的分子动力学研究

用分子动力学方法模拟了银团簇的结构与力能学.计算模拟中使用了一种基于第一性原理的原子间互作用多体势函数.通过分子动力学模拟确定了银微团簇(原子个数3～13)的稳态结构;模拟了原子个数为13～141的银FCC晶体结构理想球形团簇的力能学,发现球形银团簇形成三雏紧密结构;计算了平均结合能,给出了结合能随团簇原子数N的变化图,发现随N增大团簇结合能逐渐接近块材的数值.     

The Structure of Trichosanthin with Space Group C2 at 1. 9 Resolution

1INTRODUCTIoNInrecentyears,researchesontheribosome-inactivatingproteins(RIPs)ex-tractedfromplantshavedrawnconsiderableattentionduetotheirhighlyspecialRNAN-glycosidaseactivityandtheiranti-HlVactivity"~".Theseproteinsinacti-vateenzymicallythelargesubunitofthemammalianribosomebythereleaseofA4324fromthe28Sr-RNAt4i.lthasbeenreportedthattheseproteinsalsoactonbac-terialandplantribosomes.Theirisolationandpurificationhavebeenstudiedinde-tail,andtheirpresentstatusandfutureprospectshavealsobeen…     

具有MFI结构的La-Si ZSM-5分子筛的合成

首次合成了稀土元素掺杂的具有MFI结构的La-Si ZSM-5分子筛,并采用各种技术对所合成的分子筛进行了表征.XRD衍射表明所合成的微孔材料具有典型的MFI结构,N2吸脱附、FT-IR及SEM测试结果均表明镧原子进入了分子筛骨架.     

NMR and MO Studies on the Molecular Structure of a Fluoranthene-Benzene Complex

Summary. Fluoranthene (FA) forms a 1:1 van der Waals complex with benzene in cyclohexane. The ¹H NMR spectrum of this complex shows that the FA moiety in the complex state has five kinds of hydrogen atoms and that the ¹H NMR peaks assigned to the protons attached to the naphthalene skeleton are largely shifted to higher magnetic field on complex formation with benzene. These observations indicate that the complex takes the structure of C_S symmetry, in which the benzene molecule mainly interacts with the electronic system localized on the naphthalene moiety of FA. The present ab initio calculations reproduce well the ¹H NMR spectral shifts mentioned above and the experimentally predicted C_S structure of the complex. According to the PPP calculations for the electronic absorption spectral changes on the complex formation, the FA-benzene complex is considered to take a sandwich type structure.     

香豆素分子模板聚合物的合成与性能研究

以香豆素为模板分子, α-甲基丙烯酸(MAA)、丙烯酰胺(MA)、2-乙烯基吡啶(2-VP)和4-乙烯基吡啶(4-VP)为功能单体, 二甲基丙烯酸乙二醇酯(EGDMA)为交联剂, 利用分子模板技术分别在甲苯、甲醇、氯仿和乙腈溶剂中合成了一系列香豆素分子模板聚合物(MTP), 研究了聚合体系组成对模板聚合物吸附特性的影响. 结果表明, 在所合成的模板聚合物中, 以MAA为功能单体, 乙腈为致孔溶剂, 以1∶4∶30的摩尔比加入模板分子、MAA及EGDMA时制备的模板聚合物吸附容量高、印迹效果和选择性好. 此模板聚合物有作为白芷样品中香豆素吸附分离材料的应用前景.     

锂-,钠-,钾水化蒙脱石层间结构的分子动力学模拟

运用分子动力学(molecular dynamics, MD)方法分别研究了含有32, 64和96个水分子的Li-, Na-, K-蒙脱石层间阳离子与水分子的位置和结构. 计算结果表明蒙脱石层间阳离子位置与四面体和八面体电荷位置及离子的大小有关. 一层水合物中可以观察到三种阳离子都能和四面体电荷与八面体电荷位置分别形成内、外配位作用. 二层水合物中, 仍然可以观察到Li^＋和Na^＋与电荷位置的配位作用, 但是已经开始向层中其他方向扩散, 而K^＋仍然在粘土的表面附近. 三层水合物中, Li^＋, Na^＋开始从电荷位置和表面分离, K^＋也开始向层间其他方向扩散. 水分子在所有三种水合物中都分散于层间各个方向. 径向分布函数的分析结果表明层间三种阳离子组织水分子的能力不同, 水化作用随着阳离子半径的增大而减弱; 此外层中水分子的聚合程度随着水分子的增加而加强, 水分子的结构也不同于模拟的液体水分子的结构; 说明蒙脱石层间阳离子的溶剂化作用对水分子的组织起着重要的作用.     

人顶体酶三维结构的同源模建及其与KF950的分子对接研究

采用同源模建方法首次构建了人顶体酶的三维结构模型, 模型的可靠性经Ramachandran图和Profile_3D图验证. 采用InsightII/Binding site方法准确定位了人顶体酶的活性位点, 并研究了顶体酶重要功能残基在活性位点的立体分布. 在此基础上, 通过柔性分子对接方法首次阐明了顶体酶高效抑制剂KF950与靶酶活性位点的相互作用模式, 发现特异性的氢键相互作用是KF950产生高抑制活性的重要分子基础. 其研究结果将为合理设计新型顶体酶抑制剂, 寻找男性口服避孕药奠定坚实基础.     

Homology Modeling and Molecular Docking Studies of (S)‐Scoulerine 9‐O‐Methyltransferase from Coptis chinensis

(S)‐Scoulerine 9‐O‐methyltransferase (SMT), belonging to the S‐adenosyl‐L‐methionine (SAM)‐dependent O‐methyltransferase family, is an essential enzyme in the berberine biosynthetic pathways. In order to study the interactions of SMT with its substrate and further to understand the catalytic mechanism and substrate specificity, a three dimensional model of SMT from Coptis chinensis was constructed by homology modeling using the crystal structure of caffeic acid/5‐hydroxyferulic acid 3/5‐O‐methyltransferase (COMT) as a template. The three dimensional structure of SMT, which was mainly composed of α‐helices and some β‐sheets, was similar to that of COMT. In contrast with COMT, the non‐conserved residues in the substrate binding pocket of SMT might be responsible for their differences in the substrate specificity. Val119 and Asp254 in SMT were the key residues for orienting substrate for methylation as both residues had H‐bonds with (S)‐scoulerine. The methylation of (S)‐scoulerine involved deprotonation of the 9‐hydroxyl group by His253 and Asp254 in SMT followed by a nucleophilic attack on the SAM‐methyl resulting in the product, (S)‐tetrahydrocolumbamine.     

吲哚并喹啉衍生物与G-四链体相互作用的分子模拟研究

G-四链体是富含鸟嘌呤碱基的DNA序列通过氢键相互作用形成的四链螺旋结构. 通过小分子化合物诱导与稳定端粒G-四链体从而抑制端粒酶活性是一种新的抗癌策略. 为了研究一系列吲哚并喹啉衍生物与端粒G-四链体的相互作用, 探究其相互作用模式, 从而为实现基于G-四链体结构的药物合理设计提供依据, 使用分子对接的方法构建了吲哚并喹啉衍生物与G-四链体复合物结构, 在此基础上进行分子动力学模拟, 并使用线性相互作用能(LIE)方法计算了化合物与G-四链体的结合自由能. 结果表明: 化合物与G-四链体的主要相互作用方式由氢键、静电与π-π堆积作用构成, 侧链末端基团类型和侧链的长短是影响相互作用强弱的重要因素. 通过LIE方法计算的结合自由能与实验结果基本吻合, 相关度达到r²＝0.79. 并且, 基于预测的结合模式, 总结了拥有更高活性的新型吲哚并喹啉衍生物应具有的几个结构特征.     

Homology Modeling of Cyt2Ca1 of Bacillus thuringiensis and Its Molecular Docking with Inositol Monophosphate

Cyt2Ca1 is an insecticidal crystal protein produced by Bacillus thuringiensis ET29 during its stationary phase, and this δ‐endotoxin demonstrates remarkable insecticidal activity against not only insects of the order Coleoptera, but also against fleas, and in particular the larvae of the cat flea, Ctenocephalides felis. The first theoretical model of the three‐dimensional structure of Cyt2Ca1 was predicted and compared with Cyt2Aa, which is lethal to insect larvae. The three‐dimensional structure of the Cyt2Ca1 was obtained by homology modeling on the structures of the Cyt2Aa protein. The deduced model resembles previously reported Cyt2Aa toxin. A binding mode of inositol monophosphate as a polar head group of the putative membrane phospholipid ligand to Cyt2Ca1 was presented using molecular docking. The residues of Leu9, Glu21, Tyr23 and Gln110 of the Cyt2Ca1 toxin are responsible for the interactions with inositol monophosphate via eight hydrogen bonds. Those residues could be important for receptor recognition. This binding simulation will be helpful for the design of mutagenesis experiments aimed at the improvement of toxicity, and lead to a deep understanding of the mechanism of action of Cyt toxins.     

Molecular Structure of Neodymium Tribromide from Gas-Phase Electron Diffraction Data

The structural investigation of molecules in the vapor over neodymium tribromide was performed by synchronous gas-phase electron diffraction and mass spectrometric (GED/MS) experiments at 1110(10) K. Besides the monomeric molecules (NdBr₃), a small amount (0.7%) of the dimer (Nd₂Br₆) was detected. For NdBr₃, the thermal-average bond length r _g (Nd–Br) of 2.675(6) Å was determined. The equilibrium structure was estimated to be planar (or nearly planar) with r _e (Nd–Br) of 2.659(7) Å. Three vibrational frequencies were estimated using the GED data: ₁ = 193 cm^–1, ₂ = 35 cm^–1, ₄ = 41 cm^–1. The structural parameters of Nd₂Br₆ could not be refined and were constrained at the estimated values during the analysis.