Relative stability of major types of beta-turns as a function of amino acid composition: a study based on Ab initio energetic and natural abundance data

Folding properties of small globular proteins are determined by their amino acid sequence (primary structure). This holds both for local (secondary structure) and for global conformational features of linear polypeptides and proteins composed from natural amino acid derivatives. It thus provides the rational basis of structure prediction algorithms. The shortest secondary structure element, the beta-turn, most typically adopts either a type I or a type II form, depending on the amino acid composition. Herein we investigate the sequence-dependent folding stability of both major types of beta-turns using simple dipeptide models (-Xxx-Yyy-). Gas-phase ab initio properties of 16 carefully selected and suitably protected dipeptide models (for example Val-Ser, Ala-Gly, Ser-Ser) were studied. For each backbone fold most probable side-chain conformers were considered. Fully optimized 321G RHF molecular structures were employed in medium level [B3LYP/6-311++G(d,p)//RHF/3-21G] energy calculations to estimate relative populations of the different backbone conformers. Our results show that the preference for beta-turn forms as calculated by quantum mechanics and observed in Xray determined proteins correlates significantly.     

葫芦脲：分子识别与组装

综述了葫芦脲这一类合成受体的最新研究进展，包括葫芦脲的分子设计与合成 ，离子和分子识别，键合的热力学性质，分子组装及其功能的最新研究概况。     

Solubility Study of Nimodipine Inclusion Complexation with α- and β-Cyclodextrin and some Substituted Cyclodextrins

The solubility of nimodipine was measured in aqueous solutions of the following cyclodextrins: -cyclodextrin (-CD), hydroxypropyl--CD (HP--CD), -cyclodextrin (-CD), random substituted methyl--CD (M--CD), three hydroxypropyl--CDs (HP--CD) with mutually different average degree of substitution, and hydroxypropyl--cyclodextrin (HP--CD). From the determined linear solubility diagrams the values of the binding constant K₁₁ of the inclusion complexes of nimodipine with the respective CDs were evaluated. The -CDs efficiently solubilized sparingly soluble nimodipine, the highest value of K₁₁ was found for M--CD (1680 M^-1), followed by -CD (550 M^-1) and HP--CDs, where the higher degree of substitution lowered K₁₁. Only slight solubilization of nimodipine was observed in the solutions of the -CDs and HP--CD.     

Microfiltration of protein solutions at thin film composite membranes

An experimental study of the interaction of the enzyme yeast alcohol dehydrogenase (YADH) with polysulfone thin film composite microfiltration membranes (Dow-Danmark) has been carried out. It was found that the membranes adsorbed only 3/4 of a monolayer of the enzyme under the conditions studied. Even so, under filtration conditions, the membrane permeation rate decreased continuously with time. This decrease in permeation rate was due neither to concentration polarisation nor to protein adsorption alone. However, it could be quantified using the standard blocking filtration law, which describes a decrease in pore volume due to deposition of protein in the interior structure of the membrane. Reversal of the membrane, so that the supporting matrix faced the feed solution, gave more stable permeation rates. Implications for the microfiltration of industrial fermentation broths are discussed.     

生物催化在绿色化学和新药开发中的应用

近年来生物技术领域有了突破性进展，如: 公共基因数据库(GenBank)和蛋白质数据库(PDB)中序列的指数增长，高效基因克隆和表达平台的建立，可有效改进生物催化剂专一性、选择性和稳定性的酶定向进化技术的应用。这些进展使生物催化在化学合成中日趋重要[1]。本文综述了生物催化在如下领域的成功应用：在药物生产中用于开发经济的化学酶法合成工艺，在绿色化学领域中最大程度的减少废物的产生和危险试剂的应用，在天然化学领域中对天然产物进行修饰以发现具有更好生物活性的新药物。     

Expression and Characterization of Catalytic Domain of T Cell Protein Tyrosine Phosphatase（△TC-PTP） —— Immunohistochemical Study of △TC-PTP Expression in Non-small Cell Lung Carcinomas

This study objective was to express and characterize the catalytic domain of the human T cell protein tyrosine phosphatase（△TC-PTP） and to study immunohistochemically the expression of △TC-PTP in human non-small cell lung cancers. △TC-PTP gene was PCR amplified with the cDNA of human TC-PTP as template, and cloned into the pT7 expression vector. The recombinant pT7-△TC-PTP was expressed in E. coli Rosetta （ DE3 ） host cells and puri- fied. The enzymatic characteristics of △TC-PTP including enzyme activity and kinetics assay were measured. The antiserum was prepared by immunizing rabbit with the purified recombinant △TC-PTP. Rabbit polyclonal antibody against △TC-PTP was purified by PVDF immobilized antigen affinity chromatography. Immunohistochemical staining of lung cancer tissues was performed with antibody against △TC-PTP protein. △TC-PTP gene was correctly cloned, expressed, and purified. The recombinant △TC-PTP had a highly catalytic activity of PTPase. Squamous cell lung carcinoma showed a significantly higher expression rate of △TC-PTP （76. 92%, 10/13 ） than adenocarcinoma （57.14%, 4/7） and normal lung tissue（20%, 1/5 ）. This study represents the first demonstration that △TC-PTP is highly expressed in human squamous cell lung carcinomas. In addition, this study provides an important basis for further studying the biological function of TC-PTP and its relationship with lung carcinomas and other diseases.     

PETN基PBX结合能和力学性能的理论研究

PETN(季戊四醇四硝酸酯)是著名的硝酸酯类猛炸药,用量子力学(QM)、分子力学(MM)和分子动力学(MD)方法,计算模拟其与高聚物组成的PBX(高聚物粘结炸药)的结合能和力学性能.以AM1-MO法和MM方法取PETN与系列高聚物的尺寸匹配原子簇模型,经几何全优化计算,发现两种方法求得的结合能彼此线性相关.对PETN超晶胞及其与系列氟聚物组成的双组分PBX,实施COMPASS力场下的分子动力学(MD)周期性模拟,求得其弹性系数、拉伸模量、体模量、剪切模量和泊松比,发现添加少量高聚物确能有效改善炸药的力学性能.     

A molecular docking model of SARS-CoV S1 protein in complex with its receptor, human ACE2

The exact residues within severe acute respiratory syndrome coronavirus (SARS-CoV) S1 protein and its receptor, human ACE2, involved in their interaction still remain largely undetermined. Identification of exact amino acid residues that are crucial for the interaction of S1 with ACE2 could provide working hypotheses for experimental studies and might be helpful for the development of antiviral inhibitor. In this paper, a molecular docking model of SARS-CoV S1 protein in complex with human ACE2 was constructed. The interacting residue pairs within this complex model and their contact types were also identified. Our model, supported by significant biochemical evidence, suggested receptor-binding residues were concentrated in two segments of S1 protein. In contrast, the interfacial residues in ACE2, though close to each other in tertiary structure, were found to be widely scattered in the primary sequence. In particular, the S1 residue ARG453 and ACE2 residue LYS341 might be the key residues in the complex formation.     

Micro-Determination of Protein Containing SH– and –S–S– Groups Based on the Polarographic wave of an Electroactive Derivative

This paper presents a new simple and sensitive method for the micro-determination of protein containing SH– and –S–S– groups based on the single sweep polarographic wave of an electroactive derivative. In 0.04molL^–1 Na₃PO₄ and 0.2% ascorbic acid solution, protein is heated in a boiling water bath for 15min, the reaction product giving a sensitive reduction wave at –0.70V (vs. SCE). The wave height is linearly proportional to the concentration of protein. The calibration curves of bovine serum albumin (BSA), human serum albumin (HSA), ovalbumin (OVA) and lysozyme (Lyso) are constructed under the optimal conditions. For BSA and HSA, the linear ranges and detection limits are 0.05–24mgL^–1 and 0.02mgL^–1, respectively. The method has been applied to the determination of protein in human serum samples with satisfactory results. The mechanism of the polarographic wave was also studied, and the results show that S^2– ion is released from the protein molecule during the derivatization reaction, the wave being attributed to the reduction of HgS.