共查询到18条相似文献,搜索用时 171 毫秒
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光系统Ⅱ抑制剂—反式氰基丙烯酸酯比较分子场和电子结构研究 总被引:5,自引:0,他引:5
对反式氰基丙烯酸酯系列活性分子采用限制性系统搜索方法确定的药效团模型 ,与 9类不同骨架结构的光系统 抑制剂 DISCO模型中的反式氰基丙烯酸酯分子(M- 2 2 )的活性构象为模板所确定的药效团模型是非常相近的。对两种方法所获得的活性构象分子进行了 Co MFA研究 ,其结果是一致的。采用 PM3方法进行了量子化学计算 ,计算结果表明两种模型的构象分子具有相近的电子结构 ,根据分子静电场、立体场和电子结构探讨了该类抑制剂的构效关系。 相似文献
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使用分子动力学模拟迟火和半经验AMl方法对谷胱甘肽分子伞进行了构象分析 ,结果表明,真空下屏蔽构象和暴露构象的最低能量值相差很小(26.00kJ/mol)。 考虑溶剂效应后,屏蔽构象的能量值最高,暴露构象的能量值最低。屏蔽构象的能 量最低值高于暴露构象的能量最低值89.24kJ/mol,从理论上解释了谷胱甘肽分子 伞在水溶液中呈现暴露构象的原因。利用VolSurf参数分析了分子伞以屏蔽构象穿 透磷脂双分子层的影响因素,结果表明屏蔽构象较小的两亲矩及较大的分子褶皱程 度是其能够穿透细胞膜的主要影响因素,与构象的绝对疏水区域无关。 相似文献
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味觉化合物的构象与活性的关系许禄,姚喻元(中国科学院长春应用化学研究所应用谱学开放实验室,长春,130022)关键词味觉化合物,分子力学,构象分析分子结构和味觉的相关性是一个非常活跃的研究领域,许多人从不同的侧面进行这方面的研究,并总结出一定的规律[... 相似文献
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用密度泛函方法BHandHIYP以6-311 G(d)和6-311 G(2df)为基组对草酰溴的一价正离子(BrCO)2^ 和中性分子(BrCO)2做了构象分析,结果表明,(BrCO)^ 2和(BrCO)2都具有平面反式和交叉式两种构象。交叉式构象存在超共轭现象。此外,对草酰溴离子、中性分子各解离通道初级反应的Gibbs自由能的计算,发现草酰溴离子C-C键解离通道的反应活性总体上大于中性分子,对该反应通道进一步做了反应机理研究,证实了热力学结论。 相似文献
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A fast new approach to pharmacophore mapping and its application to dopaminergic and benzodiazepine agonists 总被引:3,自引:0,他引:3
Yvonne C. Martin Mark G. Bures Elizabeth A. Danaher Jerry DeLazzer Isabella Lico Patricia A. Pavlik 《Journal of computer-aided molecular design》1993,7(1):83-102
Summary In the absence of a 3D structure of the target biomolecule, to propose the 3D requirements for a small molecule to exhibit a particular bioactivity, one must supply both a bioactive conformation and a superposition rule for every active compound. Our strategy identifies both simultaneously. We first generate and optimize all low-energy conformations by any suitable method. For each conformation we then use ALAD-DIN to calculate the location of points to be considered as part of the superposition. These points include atoms in the molecule and projections from the molecule to hydrogen-bond donors and acceptors or charged groups in the binding site. These positions and the relative energy of each conformation are the input to our new program DISCO. It uses a clique-detection method to find superpositions that contain a least one conformation of each molecule and user-specified numbers of point types and chirality. DISCO is fast; for example, it takes about 1 min CPU to propose pharmacophores from 21 conformations of seven molecules. We typically run DISCO several times to compare alternative pharmacophore maps. For D2 dopamine agonists DISCO shows that the newer 2-aminothiazoles fit the traditional pharmacophore. Using site points correctly identifies the bioactive enantiomers of indoles to compare with catechols whereas using only ligand points leads to selecting the inactive enantiomer for the pharmacophore map. In addition, DISCO reproduces pharmacophore maps of benzodiazepines in the literature and proposes subtle improvements. Our experience suggests that clique-detection methods will find many applications in computational chemistry and computer-assisted molecular design. 相似文献
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High-performance liquid chromatographic assays for protoporphyrinogen oxidase and ferrochelatase in human leucocytes 总被引:2,自引:0,他引:2
Rapid, sensitive and specific high-performance liquid chromatographic assays are described for protoporphyrinogen oxidase and ferrochelatase in human leucocytes. The enzyme reaction products were separated and quantitated by reversed-phase high-performance liquid chromatography with fluorescence detection. The optimal pH for the protoporphyrinogen oxidase assay was 8.6 and the Michaelis constant for protoporphyrinogen IX was 9.78 +/- 0.96 microM (mean +/- S.D.). The mean (+/- S.D.) activity of protoporphyrinogen oxidase in fourteen apparently healthy subjects was 0.146 +/- 0.023 nmol protoporphyrin IX per min per mg protein. In one patient with variegate porphyria, the activity was 0.028 nmol protoporphyrin IX per min per mg protein. The optimal pH for ferrochelatase was 7.4 and with protoporphyrin and Zn2+ as substrates, the Michaelis constants were 1.49 and 8.33 microM, respectively. The mean activity of ferrochelatase in ten control subjects was 0.24 nM Zn-protoporphyrin or 2.05 nM Zn-mesoporphyrin formed per h per mg protein. 相似文献
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Koji Konomi He-Sheng Li† Norihito Kuno Masaki Furuya‡ 《Photochemistry and photobiology》1993,58(6):852-857
Abstract Treatment of imbibed embryonic axes taken from seeds of Pisum sativum with N-phenylimide S-23142, a herbicide that has been suggested to inhibit protoporphyrin synthesis, or with N -methyl mesoporphyrin IX, an inhibitor of the iron chelatase for heme, resulted in a significant decrease in the amount of spectrophotometrically detectable phytochromc in the axes in both cases. However, the amount of immunochemically detectable phytochrome was not affected by either treatment. If S-23142 inhibits the synthesis of protoporphyrin IX in pea, it appears that the conversion of protoporphyrinogen IX to protoporphyrin IX is involved in the biosynthesis of the phytochrome chromophore. The conversion of protoporphyrin IX to heme (Fe-protoporpbyrin) also appears to be a step in the biosynthesis of the chromophore, since N -methyl mesoporphyrin IX prevented the synthesis of spectrophotometrically detectable phytochrome but did not affect the magnesium chelatase activity required for the synthesis of chlorophyll in pea embryonic axes. The results suggest that protoporphyrinogen IX, protoporphyrin IX and heme are intermediates in the biogenesis of the phytochromc chromophore. The pathway to phytochromobilin might become fixed after protoporphyrin IX, being directed toward the Fe branch for heme rather than to the Mg branch for chlorophyll. 相似文献
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Combined Inhibitor Free‐Energy Landscape and Structural Analysis Reports on the Mannosidase Conformational Coordinate 下载免费PDF全文
Dr. Rohan J. Williams Javier Iglesias‐Fernández Dr. Judith Stepper Adam Jackson Dr. Andrew J. Thompson Dr. Elisabeth C. Lowe Prof. Jonathan M. White Prof. Harry J. Gilbert Prof. Carme Rovira Prof. Gideon J. Davies Prof. Spencer J. Williams 《Angewandte Chemie (International ed. in English)》2014,53(4):1087-1091
Mannosidases catalyze the hydrolysis of a diverse range of polysaccharides and glycoconjugates, and the various sequence‐based mannosidase families have evolved ingenious strategies to overcome the stereoelectronic challenges of mannoside chemistry. Using a combination of computational chemistry, inhibitor design and synthesis, and X‐ray crystallography of inhibitor/enzyme complexes, it is demonstrated that mannoimidazole‐type inhibitors are energetically poised to report faithfully on mannosidase transition‐state conformation, and provide direct evidence for the conformational itinerary used by diverse mannosidases, including β‐mannanases from families GH26 and GH113. Isofagomine‐type inhibitors are poor mimics of transition‐state conformation, owing to the high energy barriers that must be crossed to attain mechanistically relevant conformations, however, these sugar‐shaped heterocycles allow the acquisition of ternary complexes that span the active site, thus providing valuable insight into active‐site residues involved in substrate recognition. 相似文献
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Xinjian Ji Tianlu Mo Wan‐Qiu Liu Wei Ding Zixin Deng Qi Zhang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(19):6301-6304
HemN is a radical S‐adenosyl‐l ‐methionine (SAM) enzyme that catalyzes the oxidative decarboxylation of coproporphyrinogen III to produce protoporphyrinogen IX, an intermediate in heme biosynthesis. HemN binds two SAM molecules in the active site, but how these two SAMs are utilized for the sequential decarboxylation of the two propionate groups of coproporphyrinogen III remains largely elusive. Provided here is evidence showing that in HemN catalysis a SAM serves as a hydrogen relay which mediates a radical‐based hydrogen transfer from the propionate to the 5′‐deoxyadenosyl (dAdo) radical generated from another SAM in the active site. Also observed was an unexpected shunt product resulting from trapping of the SAM‐based methylene radical by the vinyl moiety of the mono‐decarboxylated intermediate, harderoporphyrinogen. These results suggest a major revision of the HemN mechanism and reveal a new paradigm of the radical‐mediated hydrogen transfer in radical SAM enzymology. 相似文献