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991.
While many structures of single protein components are becoming available, structural characterization of their complexes remains challenging. Methods for modeling assembly structures from individual components frequently suffer from large errors, due to protein flexibility and inaccurate scoring functions. However, when additional information is available, it may be possible to reduce the errors and compute near-native complex structures. One such type of information is a small angle X-ray scattering (SAXS) profile that can be collected in a high-throughput fashion from a small amount of sample in solution. Here, we present an efficient method for protein–protein docking with a SAXS profile (FoXSDock): generation of complex models by rigid global docking with PatchDock, filtering of the models based on the SAXS profile, clustering of the models, and refining the interface by flexible docking with FireDock. FoXSDock is benchmarked on 124 protein complexes with simulated SAXS profiles, as well as on 6 complexes with experimentally determined SAXS profiles. When induced fit is less than 1.5 Å interface Cα RMSD and the fraction residues of missing from the component structures is less than 3%, FoXSDock can find a model close to the native structure within the top 10 predictions in 77% of the cases; in comparison, docking alone succeeds in only 34% of the cases. Thus, the integrative approach significantly improves on molecular docking alone. The improvement arises from an increased resolution of rigid docking sampling and more accurate scoring. 相似文献
992.
Kergoat GJ Le Ru BP Genson G Cruaud C Couloux A Delobel A 《Molecular phylogenetics and evolution》2011,59(3):746-760
Though for a long time it was hypothesized that the extraordinary diversity of phytophagous insects was better explained by a synchronous pattern of co-diversification with plants, the results of recent studies have led to question this theory, suggesting that the diversification of insects occurred well after that of their hosts. In this study we address this issue by investigating the timing of diversification of a highly specialized group of seed beetles, which mostly feeds on legume plants from the tribe Indigofereae. To that purpose, a total of 130 specimens were sequenced for six genes and analyzed under a Bayesian phylogenetic framework. Based on the resulting trees we performed several analyses that allowed a better definition of the group boundaries and to investigate the status of several taxa through the use of molecular species delimitation analyses in combination with morphological evidences. In addition the evolution of host plant use was reconstructed and different molecular-dating approaches were carried out in order to assess the ages of several clades of interest. The resulting framework suggests a more ancient than previously thought origin for seed beetles, and a pattern of rapid host plant colonization. These findings call for further similar studies in other highly specialized groups of phytophagous insects. 相似文献
993.
Rowbottom DP 《Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences》2011,42(2):145-154
This paper, which is based on recent empirical research at the University of Leeds, the University of Edinburgh, and the University of Bristol, presents two difficulties which arise when condensed matter physicists interact with molecular biologists: (1) the former use models which appear to be too coarse-grained, approximate and/or idealized to serve a useful scientific purpose to the latter; and (2) the latter have a rather narrower view of what counts as an experiment, particularly when it comes to computer simulations, than the former. It argues that these findings are related; that computer simulations are considered to be undeserving of experimental status, by molecular biologists, precisely because of the idealizations and approximations that they involve. The complexity of biological systems is a key factor. The paper concludes by critically examining whether the new research programme of 'systems biology' offers a genuine alternative to the modelling strategies used by physicists. It argues that it does not. 相似文献
994.
Serpente N 《Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences》2011,42(4):403-411
Over centuries cells have been the target of optical and electronic microscopes as well as others technologies, with distinctive types of visual output. Whilst optical technologies produce images ‘evident to the eye’, the electronic and especially the molecular create images that are more elusive to conceptualization and assessment. My study applies the semiotic approach to the production of images in cell biology to capture the shift from microscopic images to non-traditional visual technologies around 1980. Here I argue that the visual shift that coincides with the growing dominance of molecular biology involves a change from iconic to symbolic forms. 相似文献
995.
流行病学是现代医学的一门重要的基础学科,也是一门应用广泛的应用学科。流行病学作为方法学在复杂疾病研究中有不可替代的作用。糖尿病具有复杂疾病属性,应该以系统的多层次的流行病学方法为研究策略。本文从流行病学与临床医学、遗传学及分子生物学交叉所形成的分支学科一临床流行病学、遗传流行病学及分子流行病学三个方面对糖尿病的研究进展作一综述,并从分子遗传学角度列举了部分糖尿病的候选基因。提出糖尿病的研究应该从宏观流行病学(如社会环境等因素的影响)和微观流行病学(如分子遗传等)结合系统地进行研究。 相似文献
996.
MicroRNAs(miRNAs)是一类非编码的内源性小RNA分子,通过调节mRNA的稳定性及蛋白翻译过程控制基因表达,从而发挥促癌或抑癌作用;研究表明,在胶质瘤的发生、进展、侵袭过程中,伴随发生了许多分子病理特征的改变,这一过程中miRNAs发挥着重要作用,本文就此方面研究进展进行综述。 相似文献
997.
胃肠道间质瘤(gastrointestinal stromal tumors,GISTs)是消化道常见的间叶肿瘤,不同于消化道真正的平滑肌瘤、神经源性肿瘤,其发生主要与Kit基因和血小板衍生生长因子受体α(platelet-derived growth factor receptor alpha,PDGFRα)基因突变有关。KIT靶点的发现使得胃肠道间质瘤治疗进入新治疗模式。伊马替尼与舒尼替尼,均为酪氨酸激酶抑制剂,分别被批准为进展期GISTs治疗的第一线及第二线靶向治疗药物。本文就GISTs的分子生物学分型以及分子靶向药物治疗进展作一概述。 相似文献
998.
目的:为了进一步增强重组蛋白质疫苗的细胞免疫应答,利用重组的IL-17作为分子佐剂,与卵清蛋白(ovalbumin,OVA)一起免疫小鼠,研究IL-17作为分子佐剂对适应性免疫的影响,探索IL-17对蛋白疫苗诱导的免疫反应,特别是细胞免疫应答的影响.方法:用OVA作为特异性蛋白疫苗,与不同剂量的IL-17联合免疫C57... 相似文献
999.
1000.