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101.
B. L. de Groot A. Amadei D. M.F. van Aalten H. J.C. Berendsen 《Journal of biomolecular structure & dynamics》2013,31(5):741-751
Abstract The recently introduced Essential Dynamics sampling method is extended such that an exhaustive sampling of the available (backbone) configurational space can be achieved. From an initial Molecular Dynamics simulation an approximated definition of the essential subspace is obtained. This subspace is used to direct subsequent simulations by means of constraint forces. The method is applied to the peptide hormone guanylin, solvated in water, of which the structure was determined recently. The peptide exists in two forms and for both forms, an extensive sampling was produced. The sampling algorithm fills the available space (of the essential coordinates used in the procedure) at a rate that is approximately six to seven times larger than that for traditional Molecular Dynamics. The procedure does not cause any significant perturbation, which is indicated by the fact that free Molecular Dynamics simulations started at several places in the space defined by the Essential Dynamics sample that complete space. Moreover, analyses of the average free Molecular Dynamics step have shown that nowhere except close to the edge of the available space, there are regions where the system shows a drift in a particular direction. This result also shows that in principle, the essential subspace is a constant free energy surface, with well-defined and steep borders, in which the system moves diffusively. In addition, a comparison between two independent essential dynamics sampling runs, of one form of the peptide, shows that the obtained essential subspaces are virtually identical. 相似文献
102.
Jian-Ping Hu Hong-Qiu He Dian-Yong Tang Guo-Feng Sun Yuan-Qin Zhang Jing Fan 《Journal of biomolecular structure & dynamics》2013,31(7):734-747
Human immunodeficiency virus type 1 (HIV-1) integrase (IN) is an important drug target for anti-acquired immune deficiency disease (AIDS) treatment and diketo-acid (DKA) inhibitors are potent and selective inhibitors of HIV-1 IN. Due to lack of three-dimensional structures including detail interactions between HIV-1 IN and its substrate viral DNA, the drug design and screening platform remains incompleteness and deficient. In addition, the action mechanism of DKA inhibitors with HIV-1 IN is not well understood. In view of the high homology between the structure of prototype foamy virus (PFV) IN and that of HIV-1 IN, we used PFV IN as a surrogate model for HIV-1 IN to investigate the inhibitory mechanism of raltegravir (RLV) and the binding modes with a series of DKA inhibitors. Firstly, molecular dynamics simulations of PFV IN, IN-RLV, IN-DNA, and IN-DNA-RLV systems were performed for 10?ns each. The interactions and inhibitory mechanism of RLV to PFV IN were explored through overall dynamics behaviors, catalytic loop conformation distribution, and hydrogen bond network analysis. The results show that the coordinated interactions of RLV with IN and viral DNA slightly reduce the flexibility of catalytic loop region of IN, and remarkably restrict the mobility of the CA end of viral DNA, which may lead to the partial loss of the inhibitory activity of IN. Then, we docked a series of DKA inhibitors into PFV IN-DNA receptor and obtained the IN-DNA-inhibitor complexes. The docking results between PFV IN-DNA and DKA inhibitors agree well with the corresponding complex of HIV-1 IN, which proves the dependability of PFV IN-DNA used for the anti-AIDS drug screening. Our study may help to make clear some theoretical questions and to design anti-AIDS drug based on the structure of IN. 相似文献
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Naveed Anjum Chikan 《Journal of biomolecular structure & dynamics》2013,31(8):1794-1804
In today’s world, the pursuit of a novel anti-cancer agent remains top priority because of the fact that the global burden of this malady is continuously increasing. Our work is no different from others in searching for new therapeutic solutions. To achieve this, we are looking into Epigenetics, the phenomenon governed by hypermethylation and hypomethylation of tumor suppressor genes and oncogenes, respectively. Our target for this study is an important intermediary methyl-CpG binding protein named kaiso. In our study, we have used the X-ray crystallographic structure of Kaiso for virtual screening and molecular dynamics simulations to study the binding modes of possible inhibitors. The C2H2 domain comprising LYS539 was used for screening the inter bio screen Database having 48,531 natural compounds. Our approach of using computer-aided drug designing methods helped us to remove the execrable compounds and narrowed our focus on a selected few for molecular simulation studies. The top ranked compound (chem. ID 28127) exhibited the highest binding affinity and was also found to be stable throughout the 20 ns timeframe. This compound is therefore a good starting point for developing strong inhibitors. 相似文献
105.
Mohammad Reza Bozorgmehr Jamshidkhan Chamani Ghodsiye Moslehi 《Journal of biomolecular structure & dynamics》2013,31(8):1669-1681
Multi-spectroscopic and density functional theory (DFT) calculations was used to study the interaction between cyclophosphamide (CYP) and aspirin (ASA) with lysozyme (LYS). The experimental results showed that fluorescence quenching of LYS by drug was a result of the formation of drug–LYS complex; static quenching was confirmed to result in fluorescence quenching. Modified Stern–Volmer plots of interaction between CYP and ASA with protein in the binary and ternary systems were used to determine the binding parameters. Molecular distances between the donor (LYS) and acceptor (CYP and ASA) for all systems were estimated according to Forster’s theory. The quantitative analysis obtained by CD spectra suggested that the presence of ASA and CYP decreased the α-helical content of LYS and induced the destabilizing of it. Theoretical studies on the interaction between LYS with ASA and CYP have been carried out using DFT at the B3LYP/6-31G level in the solvent phase. Binding energy of the mentioned complexes was calculated. It showed that tryptophan (Trp) 62 had the most affinity toward ASA and CYP. Analyzing the calculated results revealed that the five member ring of Trp has a key role in interaction of LYS with ASA and CYP. 相似文献
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【摘 要】 目的 观察和评价凝结芽孢杆菌活菌片(商品名:爽舒宝)联合热毒宁注射液治疗手足口病的临床疗效。方法 将81例手足口病患儿随机分为治疗组和对照组,治疗组41例,对照组40例,两组均给予中成药热毒宁注射液对症综合治疗。其中治疗组在治疗的同时加用凝结芽孢杆菌活菌片,1周岁以下,0.70 g/次,1周岁以上,1.05 g/次,3次/d,温水送服,疗程为7 d或治愈为止。对两组患儿疱疹、食欲、体温变化情况及食欲不振等并发症进行统计分析。结果 治疗组起效快,疱疹和腹泻消失时间、食欲和体温恢复正常时间显著短于对照组,且痊愈率、总有效率均高于对照组,差异具有统计学意义(P<0.05或0.01)。结论 凝结芽孢杆菌活菌片联合热毒宁注射液治疗手足口病疗效显著,具有积极的临床意义。 相似文献
108.
系统分析食品、药品微生物检测实验室的质量控制方法,从总体环境条件控制、微生物室管理、样品管理、仪器设备管理、人员管理、培养基质量控制、标准菌(毒)种管理、操作过程控制、记录管理等9个方面进行系统分析,对微生物实验室的质量控制工作提供系统指导,提高微生物检测结果的准确性. 相似文献
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