Forced extension of P-selectin construct using steered molecular dynamics

P-selectin, a 70-nm-long cellular adhesive molecule, possesses elastic and extensible properties when neutrophils roll over the activated endotheliam of blood vessel in inflammatory reaction. Transient formation and dissociation of P-selectin/ligand bond on applied force of blood flow induces the extension of P-selectin and relevant ligands.Steered molecular dynamics simulations were performed to stretch a single P-selectin construct consisting of a lectin(Lec) domain and an epithelial growth factor (EGF)-Iike domain, where P-selectin construct was forced to extend in water with pulling velocities of 0.005-0.05 nm/ps and with constant forces of 1000--2500 pN respectively. Resulting force-extension profiles exhibited a dual-peak pattern on various velocities, while both plateaus and shoulders appeared in the extension-time profiles on various forces. The force or extension profiles along stretching pathways were correlated to the conformational changes, suggesting that the structural collapses of P-selectin Lec/EGF domains were mainly attributed to the burst of hydrogen bonds within the major β sheet of EGF domain and the disruptions of two hydrophobic cores of Lec domain. This work furthers the understanding of forced dissociation of P-selectin/ligand bond.     

利用分子动力学方法研究吸附原子在Re（0001）表面的自扩散行为

利用分子动力学与分析型嵌入原子模型,研究了吸附原子在Re(0001)表面的自扩散行为.本文计算的扩散系数符合Arrhenius关系.扩散激活能与前因子从Arrhenius关系得到.计算的扩散激活能与低温场离子显微镜实验结果吻合,而前因子与一般理论计算结果相符.     

Interaction of aloe-emodin with human serum albumin

The presence of several high affinity binding sites on human serum albumin (HSA) makes it a possible target for many drugs. This study is designed to examine the effect of aloe-emodin on HSA by fluo-rescence, CD spectroscopy and molecular modeling. The results of fluorescence measurements sug-gested that the hydrophobic interaction was the predominant intermolecular force stabilizing the AE-HSA complex, which was in good agreement with the result of molecular modeling study. And the enthalpy change ΔH0 and the entropy change ΔS0 were calculated to be -7.041 kJ·mol-1 and 76.619 J·mol-1·K-1 according to the Van't Hoff equation. The alterations of protein secondary structure in the presence of AE in aqueous solution were quantitatively calculated from CD spectra, and the content of α-helices obviously increased.     

对乙烯基苯磺酰氯与苯乙烯的原子转移自由基共聚合制备支化聚苯乙烯

以对乙烯基苯磺酰氯作为引发剂进行了苯乙烯的原子转移自由基聚合，由于对乙烯基苯磺酰氯同时含有可聚合的乙烯基和原子转移自由基聚合引发基团，因此可以得到支化结构的聚苯乙烯。用凝胶渗透色谱对不同对乙烯基苯磺酰氯浓度下所得聚合物的分子量及其分布进行了表征，发现所得聚合物的平均分子量明显大于按照每个对乙烯基苯磺酰氯分子产生一个聚合物链计算的理论分子量，并且分子量呈多峰分布。     

分子模拟研究小分子在聚硅氧烷中扩散行为

采用分子动力学(MD)法,在298 K的温度下,对H2,He,O2,N2,CO2,CH4,H2O以及ethanol在聚二甲基硅氧烷(PDMS),聚丙基甲基硅氧烷(PPMS),聚辛基甲基硅氧烷(POMS)以及聚苯基甲基硅氧烷(PPhMS)4种聚硅氧烷体系中的扩散进行模拟.选用对凝聚态的结构和性质描述更为准确的COMPASS分子力场模型.体系进行能量优化后得到的密度和玻璃化温度的计算值和实验值的对比表明模拟体系接近于真实体系.随后进行分子动力学模拟得到小分子的运动轨迹,对小分子扩散的两种方式进行了讨论,探讨了侧链对扩散过程的影响.     

Three-dimensional recon- struction and analysis of structure characteristics on senile plaques of Alzheimer’s disease

Alzheimer‘s disease is a progressive neurodegenerative disorder characterized by the presence of senile plaques primarily composed of amyloid β in brain. Abnor-mal secretion and aggregation of amyloid β are the key events in pathogenesis of Alzheimer‘s disease. Reduction of amyloid β production and inhibition of amyloid β aggregation to form senile plaques are hopeful strategies for the treatment and prevention of Alzheimer‘s disease. In the present study, the silver and immunohistochemical staining methods were applied to discover senile plaques in the hippocampus of Alzheimer‘s disease patients, and then images were processed and three-dimensionally reconstructed by Matlab and AVS software. The structure characteristics of senile plaques were measured through correlation function calculation and fractal dimension by a computer-aided method. Diffuse plaque had no amyloid center, but classic plaque presented compact central core structure; two types of plaques were both of porous structure, but the sizes of their pores were significantly different. Furthermore, there was difference in fractal dimension value between the diffuse plaque and classic plaque in the two staining methods. The comparison of structure characteristics between two types of plaques indicated that they developed independently. Establishment of the methods for reconstructing the three-dimensional structure of senile plaque and analyzing their structure characteristics is helpful for further study on the aggregation mechanism of senile plaque.     

Stretching and imaging studies of single DNA molecules

DNA molecules were stretched on silanized mica surface with the molecular combing technique, and detected with fluorescence microscopy and atomic force microscopy. Meantime, DNA molecules were stretched with a modified dynamic molecular combing technique and studied with atomic force microscopy. The results indicate that, compared with the dynamic molecular combing technique, the modified dynamic molecular combing technique has advantages of less-sample demand and less contamination to sample; as compared with the molecular combing technique, it has better aligning effect and reproducibility. Combination of this kind of DNA molecular manipulating technique with the single DNA molecule detecting technique by atomic force microscopy and fluorescence microscopy will play an important role in the basic research of molecular dynamics and the application of gene research.     

不同侧基对磺化聚醚醚酮质子交换膜的影响

以特丁基对苯二酚和邻甲基对苯二酚分别制备两个系列磺化聚醚醚酮. 对聚合物及其膜的一些性能进行了研究, 探讨了不同取代侧基对聚合物溶解性、 热性能、 力学性能和质子传导性等性能的影响.     

Development in the research of molecular mechanism of Alzheimer’s disease

Alzheimer's disease (AD) is a kind of central nervous system disease. The cause of AD is unclear. It is found that the remarkable histopathological characters of AD are senile plaques and neurofibrillary tangles. β-amyloid plays an important role in the formation of senile plaques and the abnormal phosphorylation of Tau protein is the main reason of neurofibrillary tangles. Apolipoprotein E is correlated to AD' s access, and the third pathological character-AMY plaque perhaps represents a new cause of AD. Presenlin and proteinaceous infectious particles are also related with AD. A summary of molecular mechanism for AD and the development of research is presented.     

Stepwise prediction and statistical screening: B-cell epitopes on neuraminidase of human avian H5N1 virus

The B-cell epitopes of virus are associated with the antiviral drug and the vaccine screening. As the nucleotide sequences of neuraminidase （NA） of stain GD-01-06 were sequenced, we predicted the a-helix and β-fold structure and the indexes of the flexible regions of secondary structure of NA with methods of the Hydrophilicity plot by Kyte-Doolittle, the Surface probability plot by Emini and the An- tigenic index by Jameson-Wolf, and then screened statistically the parameters to predict B-cell epi- topes by the Hierarchical cluster and the Bivariate correlation and the quartiles with SPSS 13.0. The impact of variation of amino acids in NA on its epitopes was analyzed. The predictive results were evaluated by Wu＇s Antigenic Index and SWISS-MODEL. We found that the most possible epitopes on NA were located within or nearby its N-terminal Nos. 120--137, 81--84, 408--415, 273--282, 429--432, 356--368, 46--55, 146--155, 341 --350 and 198--209, which were the dominant regions of NA epitopes. Peptide 120--137 including the glycoprotein domain （NGT126 128） was first chosen as the B-cell epitopes on NA. NA in H5N1 strain isolated after 2003 lacked in No. 53 amino acid （I）, resulting in an increase in the surface flexible region of NA in GD-01-06 and an enlargement to their epitope regions （VEP48-48→ VEPISNTNFL46-55）. Conclusively, prediction of the B-cell epitopes on the NA based on multiple pa- rameters is useful for researches on the molecular immunology and drug screening and immuno-prophylaxis. A deletion of No. 53 amino acid （I） in NA in strain GD-01-06 might increase its anti- genicity.     

Phase boundary sliding model controlled by diffusionsolution zone in superplastic deformation

With scanning electron microscope (SEM), the surface morphology of phase boundary sliding (PBS) in superplastic deformation (SPD) of Zn-Al alloy and the diffusion behavior of Zn, Al interfaces in their powers' sintering have been investigated. The results show that Zn-Al eutectoid microstructure can be achieved through their powders' sintering, and the diffusion characteristic between Zn and Al is just a demonstration of Kirkendall effect, in which Zn can dissolve into Al whereas A1 can hardly dissolve into Zn. During sintering, a diffusion-solution zone ?′ has formed and subsequently transformed into a eutectoid microstructure in the cooling process. The superplastic deformation mechanism of Zn-Al eutectic alloy is phase boundary sliding which is controlled by the diffusion-solution zone ?′. If the diffusion-solution zone ?′ is unsaturated, it will have much more crystal defects and the combination between ?′ and phase ? is weak, thus the process of phase boundary sliding becomes easily; on the contrary, if the diffusion-solution zone ?′ becomes thick and saturated, the sliding will be difficult.     

HIV-1蛋白酶与抑制剂结合中桥接水分子作用的QM/MM研究

对HIV-1蛋白酶与抑制剂2AH和4AH结合的两个复合物体系进行了水溶液环境下量子力学分子力学混合方法(hybrid QM/MM)的1ns分子动力学模拟,用MM-GBSA方法得到桥接水分子W301与HIV-1蛋白酶和抑制剂结合体的结合自由能分别为-24.93 kJ/mol和-20.29 kJ/mol,表明W301在抑制剂和HIV-1蛋白酶结合的过程中起到了不能被忽略的作用。     

MD模拟温度对TATB和TATB/F2311 PBX力学性能的影响

为探讨高聚物粘结炸药(polymer-bonded explosive,PBX)的力学性能和结合能随温度变化的规律,该文用分子动力学(MD)方法和compass力场,在NPT系综下对钝感炸药TATB(1,3,5-三氨基-2,4,6-三硝基苯)及其与氟橡胶F2311所构成的阳X,进行不同温度下的周期性模拟.结果表明:与TATB单体炸药相比,PBX的力学性能显著改善,拉伸模量、体积模量和剪切模量均有所下降;随温度升高,PBX的刚性减小,弹性增强;结合能随温度升高呈先降后升再降的复杂变化趋势.     

NMR and IR investigations of ternary inclusion complexes among β-cyclodextrin, rare earth metal ions, and naphthalenediamines

Ternary inclusion complexes β-cyclodextrin (β-CD), rare earth metal ions (YbCl₃, YCl₃), and 1,8-naphthalene- diamine/1,5-naphthalenediamine are synthesized in basic aqueous media, which are characterized via ¹H NMR and IR spectroscopy. The stoichiometric proportion of β-CD:YbCl₃:1,5-naphthalenediamine is 2:1:2, that of β-CD:YCl₃:1,8-naphthalenediamine is 2:1:1, and that of β-CD:YbCl₃:1,8-naphthalenediamine is 2:1:1. The IR spectroscopy of the ternary inclusion complexes in the range of 935–1 000 cm⁻¹ reveals the existence of the coordinate bond M—O or M—N. The possible conformations of the ternary inclusion complexes are depicted. Biography: JIANG Huiming(1972–), male, Associate professor, research direction: molecular complex chemistry, supramolecular chemistry.     

Computation of the acoustic nonlinearity parameter in organic liquid binary mixtures

Based on Jacobson’s molecular free length theory in liquids and the relationship between the ultrasonic velocity and the molecular free length in organic liquids, the equation of the acoustic nonlinearity parameter in organic liquid binary mixtures is derived. The calculated values from the equation are in good agreement both with those from Apfel’s and from Sehgal’s mixture laws.     

Separation and analysis of the soluble trimer of Aβ1-40 and its effects on the rise in intracellular calcium

Alzheimer’s disease (AD) is one of the progressive neurodegenerative diseases associated with protein conformational transition, generally known as protein conformational disorders[1]. The general characteriza- tions of AD are the intracellular fibrillar…     

Molecular dynamics study on BPTI aqueous solution by ABEEM/MM fluctuating charge model

Molecular dynamics simulation on BPTI （biovine pancreatic trypsin inhibitor） aqueous solution has been performed for the first time in terms of the atom-bond electronegativity equalization method fused with molecular mechanics （ABEEM/MM）. The simulated parameters including ABEEM parameters and force field parameters have been tested. Some structural properties including root-mean-square deviations of atomic coordinates and radial distribution functions were studied by ABEEM/MM fluctuating charge method. The results demonstrate that this model can obtain reasonable structural properties compared with experimental crystal data. The radial distribution functions indicate that ABEEM/MM method can well embody the electrostatic polarizations between protein molecule and its surrounding solvent waters.     

诺氟沙星的密度泛函研究

以诺氟沙星为研究对象,采用密度泛函理论的B3LYP/6-311+G(d,p)方法,进行分子结构全优化,并对红外光谱(IR)和拉曼光谱(Raman)、前线轨道(最高占据轨道HOMO、最低空轨道LUMO)、净电荷分布进行了量子力学计算.根据红外光谱(IR)和拉曼光谱(Raman)的计算结果,对振动模式进行了指认;根据前线轨道(HOMO、LUMO)、净电荷分布的计算结果,讨论了诺氟沙星的HOMO、LUMO和分子表面电势的特点.采用密度泛函理论的B3LYP/6-311+G(2d,p)方法,进行分子结构全优化,使用GIAO方法计算得到核磁共振谱(NMR),并对谱图数据进行了分析讨论.     

水分子簇结构改变的分子动力学

为揭示水分子团簇形成的理论，在制备具有生物功能的六环结构水的工作基础上，应用量子力学的理论方法，对单个水分子转动惯量进行模拟计算。结果表明，当水分子的键长、键角和偶极矩发生变化时，其转动能谱也随之变化。用分子动力学方法分析了水分子簇微观结构改变后的六环水中原子运动方式，从理论上证明了六环结构水具有稳定存在的动力学特征。     

Cell adhesion receptors and cancer

Cell-to-cell and cell-to-extracellular matrix (ECM) interactions in the functions of cell adhesion and signal transduction are important in global control of cell phenotypes and cell behavior and are crucial for maintenance of homeostasis and structural/functional stabilization of tissues and organs. Cell adhesion receptors are recognized as the molecular basis of cell adhesion. Cadherin and Integrin are widely expressed adhesion receptors in most tissues. They are transmembrane glycoproteins which, through their cytoplasmic domain, bind to many proteins at the inner surface of cell membrane to form molecule-linkage complexes and then connect with the cytoskeleton. Through cell adhesion receptors a network functioning as cell adhesion and signal transduction is organized between tissue cells and cell-ECM. In this regard cell adhesion receptors play an important role in regulation of morphogenesis, cell-cell recognition, cell migration, cell sorting and the determination of cell's fate in development. They mediate cell functions and their fault expression is intimately correlated with development of disorders like cancer. Several isoforms of Integrin were found to have tumor suppressor effect. Some components in the molecule-linkage of focal contact are actin-binding proteins as well as substrates of kinase in the Integrin initiated signal pathway to play a role as signal transducer. Some of these molecules exhibited tumor suppressor effect too. Decreased expression of E-Cadherin has been demonstrated in many epithelium originated carcinomas. Cadherin associated membrane adhesion plaque molecule β-Catenin is also involved in the oncogene Wnt signal pathway. Both E-Cadherin and β-Catenin were proved respectively with tumor suppressor effect against invasiveness and metastasis. That Cadherin is important for the posttranslationally functional expression of Connexin has been supported by evidence from developmental biology and cancer cell differentiation studies to suggest that some sort of interrelation feedback control exists between the two signal pathways.