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Jana Selent Agnieszka A. Kaczor Ramon Guixà-González Pau Carrió Manuel Pastor Cristian Obiol-Pardo 《Journal of molecular modeling》2013,19(4):1507-1514
Survivin, the smallest inhibitor of apoptosis protein (IAP), is a valid target for cancer research. It mediates both the apoptosis pathway and the cell cycle and has been proposed to form a complex with the cyclin-dependent kinase protein CDK4. The resulting complex transports CDK4 from the cytosol to the nucleus, where CDK4 participates in cell division. Survivin has been recognized as a node protein that interacts with several partners; disruption of the formed complexes can lead to new anticancer compounds. We propose a rational model of the survivin/CDK4 complex that fulfills the experimental evidence and that can be used for structure-based design of inhibitors modifying its interface recognition. In particular, the suggested complex involves the alpha helical domain of survivin and resembles the mode of binding of survivin in the survivin/borealin X-ray structure. The proposed model has been obtained by combining protein–protein docking, fractal-based shape complementarity, electrostatics studies and extensive molecular dynamics simulations. Figure
Proposed model of the survivin/CDK4 complex with a close view of the best model refined through molecular dynamics simulations 相似文献
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It is well-known that word frequencies arrange themselves according to Zipf''s law. However, little is known about the dependency of the parameters of the law and the complexity of a communication system. Many models of the evolution of language assume that the exponent of the law remains constant as the complexity of a communication systems increases. Using longitudinal studies of child language, we analysed the word rank distribution for the speech of children and adults participating in conversations. The adults typically included family members (e.g., parents) or the investigators conducting the research. Our analysis of the evolution of Zipf''s law yields two main unexpected results. First, in children the exponent of the law tends to decrease over time while this tendency is weaker in adults, thus suggesting this is not a mere mirror effect of adult speech. Second, although the exponent of the law is more stable in adults, their exponents fall below 1 which is the typical value of the exponent assumed in both children and adults. Our analysis also shows a tendency of the mean length of utterances (MLU), a simple estimate of syntactic complexity, to increase as the exponent decreases. The parallel evolution of the exponent and a simple indicator of syntactic complexity (MLU) supports the hypothesis that the exponent of Zipf''s law and linguistic complexity are inter-related. The assumption that Zipf''s law for word ranks is a power-law with a constant exponent of one in both adults and children needs to be revised. 相似文献
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Isabel Ferrera Ramon Massana Vanessa Balagué Carles Pedrós-Alió Olga Sánchez Jordi Mas 《Biofouling》2013,29(3):349-357
Phototrophic biofilms are used in a variety of biotechnological and industrial processes. Understanding their structure, ie microbial composition, is a necessary step for understanding their function and, ultimately, for the success of their application. DNA analysis methods can be used to obtain information on the taxonomic composition and relative abundance of the biofilm members. The potential bias introduced by DNA extraction methods in the study of the diversity of a complex phototrophic sulfide-oxidizing biofilm was examined. The efficiency of eight different DNA extraction methods combining physical, mechanical and chemical procedures was assessed. Methods were compared in terms of extraction efficiency, measured by DNA quantification, and detectable diversity (16S rRNA genes recovered), evaluated by denaturing gradient gel electrophoresis (DGGE). Significant differences were found in DNA yields ranging from 116 ± 12 to 1893 ± 96 ng of DNA. The different DGGE fingerprints ranged from 7 to 12 bands. Methods including phenol–chloroform extraction after enzymatic lysis resulted in the greatest DNA yields and detectable diversity. Additionally, two methods showing similar yields and retrieved diversity were compared by cloning and sequencing. Clones belonging to members of the Alpha-, Beta- and Gamma- proteobacteria, Bacteroidetes, Cyanobacteria and to the Firmicutes were recovered from both libraries. However, when bead-beating was applied, clones belonging to the Deltaproteobacteria were also recovered, as well as plastid signatures. Phenol–chloroform extraction after bead-beating and enzymatic lysis was therefore considered to be the most suitable method for DNA extraction from such highly diverse phototrophic biofilms. 相似文献
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A. R. Srinivasan Ramon Torres William Clark Wilma K. Olson 《Journal of biomolecular structure & dynamics》2013,31(3):459-496
Abstract A series of potential energy calculations have been carried out to estimate base sequence dependent structural differences in B-DNA. Attention has been focused on the simplest dimeric fragments that can be used to build long chains, computing the energy as a function of the orientation and displacement of the 16 possible base pair combinations within the double helix. Calculations have been performed, for simplicity, on free base pairs rather than complete nucleotide units. Conformational preferences and relative flexibilities are reported for various combinations of the roll, tilt, twist, lateral displacement, and propeller twist of individual residues. The predictions are compared with relevant experimental measures of conformation and flexibility, where available. The energy surfaces are found to fit into two distinct categories, some dimer duplexes preferring to bend in a symmetric fashion and others in a skewed manner. The effects of common chemical substitutions (uracil for thymine, 5-methyl cytosine for cytosine, and hypoxanthine for guanine) on the preferred arrangements of neighboring residues are also examined, and the interactions of the sugar-phosphate backbone are included in selected cases. As a first approximation, long range interactions between more distant neighbors, which may affect the local chain configuration, are ignored. A rotational isomeric state scheme is developed to describe the average configurations of individual dimers and is used to develop a static picture of overall double helical structure. The ability of the energetic scheme to account for documented examples of intrinsic B-DNA curvature is presented, and some new predictions of sequence directed chain bending are offered. 相似文献
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Molecular Dynamics Simulations of Rhodopsin Point Mutants at the Cytoplasmic Side of Helices 3 and 6
Arnau Cordomí Eva Ramon Pere Garriga Juan J. Perez 《Journal of biomolecular structure & dynamics》2013,31(6):573-587
Abstract The present work reports on a structural analysis carried out through different computer simulations of a set of rhodopsin mutants with differential functional features in regard to the wild type. Most of these mutants, whose experimental features had previously been reported [Ramon et al. J Biol Chem 282, 14272–14282 (2007)], were designed to perturb a network of electrostatic interactions located at the cytoplasmic sides of transmembrane helices 3 and 6. Geometric and energetic features derived from the detailed analysis of a series of molecular dynamics simulations of the different rhodopsin mutants, involving positions 134(3.49), 247(6.30), and 251(6.34), suggest that the protein structure is sensitive to these mutations through the local changes induced that extend further to the secondary structure of neighboring helices and, ultimately, to the packing of the helical bundle. Overall, the results obtained highlight the complexity of the analyzed network of electrostatic interactions where the effect of each mutation on protein structure can produce rather specific features. 相似文献