共查询到20条相似文献,搜索用时 9 毫秒
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A. V. Sulimov D. C. Kutov E. V. Katkova O. A. Kondakova V. B. Sulimov 《Russian Chemical Bulletin》2017,66(10):1913-1924
The following reasons limiting the accuracy of calculations of the protein—ligand binding energy by the molecular docking programs are considered: the limited facilities of algorithms of finding a global minimum on a complicated multi-dimensional protein—ligand energy surface, restrictions on the degrees of freedom of a protein—ligand system including docking into a rigid protein, inadequacy of the existing force fields, a lack of taking into account the solvent or too rough allowance for the solvent in the docking procedure, a lack of the local energy optimization in the docking process, an inaccuracy of the construction of models of a target protein and a ligand, simplification of the calculation method of the Gibbs free energy of a molecular system, and limited computer resources for docking of one ligand. A new approach to the development of the new generation of docking programs is proposed. The approach allows one to remove step-by-step the existing simplifications and to increase considerably the accuracy of the whole docking process, including the calculation accuracy of the protein—ligand binding energy. The results of the study are presented and demonstrate the computational feasibility of the assigned docking problem. 相似文献
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Yong Jiao Pin Yang 《中国化学快报》2007,18(3):357-360
The inhibitory mechanism of copper(Ⅱ) on the aggegation of amyloid β-peptide (Aβ) was investigated by molecular dynamics simulations. The binding mode ofcopper(Ⅱ) with Aβ is characterized by the imidazole nitrogen atom, Nπ, of the histidine residue H 13, acting as the anchoring site, and the backbone's deprotoned amide nitogen atoms as the main binding sites. Drove by the coordination bonds and their induced hydrogen bond net, the conformations of Aβ converted from β-sheet non-β-sheet conformations, which destabilized the aggregation of Aβ into fibrils. 相似文献
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In this paper, a kind of gold nanoparticle (GNP)-based colorimetric assay has been developed for studying the reversible interaction of β-amyloid peptide (Aβ) with Cu2+ and Zn2+, and quantitatively analyzing four inhibitors (i.e., EDTA, EGTA, histidine and clioquinol) of Cu2+/Zn2+ induced Aβ assembly. The inhibition efficiencies (e.g., half maximal inhibitory concentration, IC50 value) of these inhibitors could be measured in this work. As far as we know, these IC50 values were reported at the first time. In this assay, the streptavidin conjugated GNPs (SA-GNPs) were employed as indicators to monitor the Cu2+/Zn2+ induced aggregating/disaggregating behaviors of biotin modified β-amyloid 1–16 peptides (Aβ1–16(biotin)). Because of high affinity of streptavidin (SA) with biotin, the aggregating/disaggregating of Aβ1–16(biotin) results in the significant color change of SA-GNPs. Furthermore, we demonstrate that the assay can be used as an effective tool for designing anti-dementia drugs through quantitative analysis of the interactions of four representative inhibitors with Cu2+/Zn2+ induced Aβ assembly. 相似文献
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A scries of polymeric adsorbents with peptide pendants were designed as the artificial receptors of β-laetarn antibiotics by mimicking the structures of binding site in β-lactamases.Crosslinked poly(N,N-dimethyl acry-lamide) gel as a carrier was prepared by suspension copolyrnerization of N,N-dimethyl acrylamide and N,N-bisacryl-diaminoethane and then functionalized with ethylenediamine after partial hydrolysis.Using solid-phase peptide synthesis with symmetrical anhydride of protected amino acid step by step,various peptide pendants were respectively anchored onto the functionalized carrier.The adsorption properties of these peptide-containing adsorbents for β-lactam antibiotics such as ampicillin and cefotaxime were then studied.The results showed that only those adsorbents in which peptide chains contained more than one lysine residues could obviously adsorb both β-lactams and that static interaction as well as hydrogen bond played an important role during the adsorption 相似文献
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Chunyi Jiang Yu Feng Xiaotong Huang Yechun Xu Yaping Zhang Naiming Zhou Xu Shen Kaixian Chen Hualiang Jiang Dongxiang Liu 《Analytical and bioanalytical chemistry》2010,396(5):1745-1754
Aβ1–42 is the proteolytic cleavage product of cleavage of the amyloid precursor protein by β- and γ-secretases. The aggregation
of Aβ1–42 plays a causative role in the development of Alzheimer’s disease. To lock Aβ1–42 in a homogenous state, we embedded the Aβ1–42 sequence in an unstructured region of Bcl-xL. Both the N-terminus and the C-terminus of Aβ1–42 were constrained in the disordered region, whereas the conjunction did not introduce any folding to Aβ1–42 but maintained the sequence as a monomer in solution. With Bcl-xL-Aβ42, we developed an enzyme-linked immunosorbent assay to compare the affinity of compounds for monomeric Aβ1–42. Bcl-xL-Aβ42 was coated on a microplate and this was followed by incubation with different concentrations of compounds. Compounds binding
to Leu17-Val24 of Aβ1–42 inhibited the interaction between Bcl-xL-Aβ42 and antibody 4G8. The method can not only reproduce the activities of the reported Aβ1–42 inhibitors such as dopamine, tannin, and morin but can also differentiate decoy compounds that do not bind to Aβ1–42. Remarkably, using this method, we discovered a new inhibitor that binds to monomeric Aβ1–42 and inhibits Aβ1–42 fibril formation. As the structure of Bcl-xL-Aβ42 monomer is stable in solution, the assay could be adapted for high-throughput screening with a series of antibodies that
bind the different epitopes of Aβ1–42. In addition, the monomeric form of the Aβ1–42 sequence in Bcl-xL-Aβ42 would also facilitate the identification of Aβ1–42 binding partners by coimmunoprecipitation, cocrystallization, surface plasmon resonance technology, or the assay as described
here. 相似文献
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Taxol is one of the most important anti-cancer drugs. The interaction between different variants of Taxol, by altering one of its chiral centers at a time, with β-tubulin protein has been investigated. To achieve such goal, docking and molecular dynamics (MD) simulation studies have been performed. In docking studies, the preferred conformers have been selected to further study by MD method based on the binding energies reported by the AutoDock program. The best result of docking study which shows the highest affinity between ligand and protein has been used as the starting point of the MD simulations. All of the complexes have shown acceptable stability during the simulation process, based on the RMSDs of the backbone of the protein structure. Finally, MM-GBSA calculations have been carried out to select the best ligand, considering the binding energy criteria. The results predict that two of the structures have better affinity toward the mentioned protein, in comparison with Taxol. Three of the structures have affinity similar to that of the Taxol toward the β-tubulin. 相似文献
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ZHANG YiMing YANG XuShu SUN Cheng & WANG LianSheng School of Basic Medical Sciences Nanjing Medical University Nanjing China School of Pharmacy China State Key Laboratory of Pollution Control Resources Reuse School of Environment Nanjing University Nanjing China 《中国科学B辑(英文版)》2011,(1)
Estrogen compounds may pose a serious threat to the health of humans and wildlife.The estrogen receptor (ER) exists as two subtypes,ERβ and ERβ.Compounds might have different relative affinities and binding modes for ERβ and ERβ.In this study,the heuristic method was performed on 31 compounds binding to ERβ to select 5 variances most related to the activity (LogRBA) from 1524 variances,which were then employed to develop the best model with the significant correlation and the best predictive power (r2 = 0.8... 相似文献
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Valensin D Migliorini C Valensin G Gaggelli E La Penna G Kozlowski H Gabbiani C Messori L 《Inorganic chemistry》2011,50(15):6865-6867
The reactions of human β-amyloid peptide 1-28 (Aβ28) with Al(III) and Fe(III) ions were investigated by (1)H NMR and electrospray ionization mass spectrometry (ESI-MS) under pH conditions close to physiological ones. (1)H NMR titrations, performed in the 5.3-8.0 pH range, revealed that no measurable amounts of Aβ28-Al(III) or Aβ28-Fe(III) adducts are formed; such metal adducts could not be obtained even by changing a number of experimental conditions, e.g., temperature, buffer, nature of the salt, etc. These observations were later confirmed by ESI-MS. It is thus demonstrated that Aβ28, at physiological pH, is not able to form binary complexes with Al(III) and Fe(III) ions of sufficient stability to compete with metal hydroxide precipitation. The biological implications of these findings are discussed in the frame of current literature. 相似文献
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An efficient synthesis of high generation conjugated polyphenylene dendrimer-based β-diketones was investi- gated using simple synthetic methods. The new dendrimer-based β-diketones were characterized by NMR, MS and elemental analysis. The UV-Vis and fluorescence spectra of these β-diketones in different solvents were investigated The photoluminescent (PL) quantum yield and TG and DSC curves were also investigated. A new intermediate, 1-bromo-3,5-diiodobenzene, was developed to synthesize high generation dendrimers with good yields. 相似文献
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A novel method for the synthesis of N-monosubstituted aniline and its derivatives via β-cyclodextrin (CD) host-guest complexes has been presented. The mild reaction gives the title compounds with high selectivity in good yields of 90-98%. 相似文献
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The intermolecular reductive coupling of 1,1-diary1-2,2-drcyanoethylenes with cinnamic esters promoted by samarium( Ⅱ)iodide was studied.Functionalized cyclopentenylamine derivatives were prepared in good yields under neutral and mild conditions. 相似文献
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Chao Feng Zhang Li Fan Pin Yang 《中国化学快报》2007,18(1):97-98
Zinc may play a role as a co-factor in the pathogenesis of Alzheimer's disease(AD)through influencing the conformation and neurotoxicity of amyloidβ-protein(Aβ).Using the fluorescamine assay,we show for the first time that Zn~(2 )induced Aβ(10-21) aggregate in a concentration-dependent manner.These results indicate that Aβ(10-21)can be used as an in vitro model in Zn~(2 )- induced Aβaggregation and that the region 10-21 to be the minimal fragment of zinc-binding domain of full length Aβ(1-42). 相似文献
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The supramolecular interaction of gemfibrozil with β-cyclodextrin (β-CD) was studied by spectrofluorimetry. The mechanism of the inclusion was discussed by spectrofluoremetry, infrared spectrum and ^1H NMR spectrum. The results showed that a 1 : 1 (β-CD : gemfibrozil) complex was formed with an apparent association constant of 3.844 × 10^3 L·mol^-1. Based on the enhancement of the fluorescent intensity of gemfibrozil, a spectrofluorimetric method for the determination of gemfibrozil in bulk aqueous solution in the presence of β-CD was developed. The linear range was 3.30 ng·mL^- 1 -6.00 ug·mL^-1 with the detection limit of 0.980 ng·mL^-1. There was no interference from the excipients normally used in tablet composition and the serum main compositions. The proposed method was then successfully applied to the determination of gemfibrozil in capsules and serum. 相似文献
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Conjugate addition of indoles to a variety of α,β-unsaturated ketones (chalcones) mediated by a catalytic amount of KHSO4 at room temperature under ultrasonic conditions to afford the corresponding Michael adducts in good to excellent yields was reported. 相似文献
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<正>A highly effective,new chiral 1,2,3,4-tetrahydroisoquinoline catalyst 1 for the diethylzinc addition to aryl aldehydes has been investigated.Using 10 mol%of this chiral catalyst,secondary alcohols can be obtained in up to 87%yield and 99.5%ee under mild conditions. 相似文献
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《化学学报》2012,70(11)
介孔分子筛MCM-41依次与3-氯丙基三乙氧基硅烷、环己二胺和三唑醛反应,得到席夫碱修饰的新型介孔分子筛MCM-41催化剂.通过傅里叶变换红外光谱(FTIR)和X射线多晶衍射(XRD)等方法对所得催化剂进行表征.以过氧化氢为氧源,介孔分子筛MCM-41负载的席夫碱为催化剂,研究了α,β-不饱和酮的环氧化反应,考察了金属盐、溶剂、催化剂用量、反应时间等因素对环氧化反应的影响.结果表明,在室温下乙腈溶剂中,α,β-不饱和酮的环氧化反应在短时间内均以很高的产率(高达99%)得到了相应的产物.同时,对催化剂的重复利用进行了研究,发现重复使用四次,仍能以较高产率得到环氧化产物. 相似文献
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Xiao-ming Chen Hai-yang Yang Ping-sheng He 《化学物理学报(中文版)》2009,22(5):541-544
PVP/SDS complex was applied as a probe to study the interaction between β-cyclodextrin (β-CD) and sodium dodecyl sulfate (SDS) in aqueous solution. It has been found that a critical concentration, namely cs, exists in the relative viscosity of solution containing PVP/SDS complex versus β-CD concentration plot. As the β-CD concentration is less than cs, the relative viscosity of solution decreases sharply by adding β-CD into solution successively. On the other hand, as the β-CD concentration is greater than cs, the relative viscosity of solution increases gradually by adding β-CD into solution. The decrease of the relative viscosity of solution containing PVP/SDS in the presence of β-CD is just due to the inclusion complex of β-CD with the guest molecule SDS. And, this inclusion interaction takes down SDS from the PVP chains in solution. The ratio of the host molecule β-CD to the guest molecule SDS can be calculated from Cs. In our experiment the inclusion ratio of β-CD to SDS is 1/1. The further experimental results indicate that cs is associated with SDS but free from PVP in PVP/SDS complex. However, the inclusion ratio of β-CD to SDS has proved to be independent of either SDS or PVP in PVP/SDS complex. 相似文献
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Density functional theory (DFT) B3LYP method is used to theoretically investigate the adsorption conformations of H2O and glycol on the relaxation surface of β-Si3N4(0001) with cluster models. For H2O, the most stable structure is that adsorbed through the H atom lying above a N(3) site of the relaxation surface of β-Si3N4(0001); while for glycol, it is the one adsorbed via the H atom lying above the center of Si(2) and N(3) of the same relaxation surface. The adsorption energy, adsorption bond and transfer electrons of the two adsorbed substances prove that glycol is easy to be adsorbed on the relaxation surface of β-Si3N4(0001). 相似文献