1,720,979 research outputs found
Electrostatic versus nonelectrostatic effects in DNA sequence discrimination by divalent ions Mg2+ and Mn2+
No full textMg2+ and Mn2+ ions are critical to the functioning of phosphoryl transfer enzymes, such as restriction endonucleases. Although these ions play similar roles in the chemical steps, they govern substrate specificity via modulating sequence discrimination by up to a factor of 105 with Mg2+ and only up to a factor of 10 with Mn2+. To explain whether such diversity originates in fundamental differences in the electronic structures of the nucleobase - hydrated-metal ion complexes, structures and interaction energies were determined at the density functional (DFT) and second-order Møller-Plesset (MP2) levels of theory. Although both metal ions favor identical binding sites, Mn2+ complexes exhibit greater distortions from the ideal octahedral geometry and larger variability than the corresponding Mg2+ systems. In inner-shell complexes, with direct contact between the metal and the nucleobase, Mg2+ is preferred over Mn2+ in the gas phase, due primarily to nonelectrostatic effects. The interaction energies of the two metal ions are more similar in the outer-shell complexes, likely due to reduced charge transfer between the hydrated metal ion and the base moieties. Inclusion of solvation effects can amplify the relative nucleobase preferences of Mg2+ and Mn2+, indicating that bulk hydration modulates the balance between electrostatic and nonelectrostatic terms. In most cases, the base substitutions in solution are facilitated more by Mn2+ than by Mg2+. Electrostatic properties of the environment were demonstrated to have a major influence on the nucleobase preferences of the two metal ions. Overall, quantum chemical calculations suggest that the contrasting selectivity of Mg2+ and Mn2+ cofactors toward nucleobases derives from the larger flexibility of the Mn 2+ complexes accompanied by the excessive polarization and charge-transfer effects as well as less favorable solvation. © 2007 American Chemical Society
Phosphorylation-induced transient intrinsic structure in the kinase-inducible domain of CREB facilitates its recognition by the KIX domain of CBP
No full textPhosphorylation at Ser-133 of the kinase inducible domain of CREB (KID) triggers its binding to the KIX domain of CBP via a concomitant coil-to-helix transition. The exact role of this key event is still puzzling: it does not switch between disordered and ordered states, nor its direct interactions fully account for selectivity. Hence, we reasoned that phosphorylation may shift the conformational preferences of KID towards a binding-competent state. To this end we investigated the intrinsic structural properties of the unbound KID in phosphorylated and unphosphorylated forms by simulated annealing and molecular dynamics simulations. Although helical populations show subtle differences, phosphorylation reduces the flexibility of the turn segment connecting the two helices in the complexed structure and induces a transient structural element that corresponds to its bound conformation. It is stabilized by the pSer-133-Arg-131 interaction, which is absent from the unphosphorylated KID. Diminishing this coupling decreases the 3.1 kcal/mol contribution of pSer-133 to the binding free energy (ΔGbind) of the phosphorylated KID to KIX by 1.1 kcal/mol, as computed in reference to Ser-133. In a binding competent form of the S133E KID mutant, the contribution of Glu-133 to ΔG bind is by 1.5 kcal/mol smaller than that of pSer, suggesting that altered structural properties due to pSer → Glu replacement impair the binding affinity. Thus, we propose that phoshorylation contributes to selectivity not merely by the direct interactions of the phosphate group with KIX, but also by promoting the formation of a transient structural element in the highly conserved turn segment. © 2006 Wiley-Liss, Inc
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Evaluating boundary dependent errors in QM/MM simulations
No full textHybrid quantum mechanics/molecular mechanics (QM/MM) simulations provide a powerful tool for studying chemical reactions, especially in complex biochemical sy. In most works to date, the quantum region is kept fixed throughout the simulation and is defined in an ad hoc way based on chemical intuition and available computational resources. The simulation errors associated with a given choice of the quantum are, however, rarely assessed in a systematic manner. Here we study the dependence of two relevant quantities on the QM region size: the force error at the center of the QM region and the free energy of a proton transfer reaction. Taking lysozyme a our model system, we find that in an apolar region the average force error rapidly decreases with increasing QM region size. In contrast, the average force error at the polar active site is considerably higher, exhibits large oscillations and decreases mslowly, and may not fall below acceptable limits even for a quantum region radius of 9.0 Å. Although computation of free energies could only be afforded until 6.0 Å, results were found to change considerably within these limits. These errors demonstratthat the results of QM/MM calculations are heavily affected by the definition of the QM region (not only its size), and a convergence test is proposed to be a part of setting up QM/MM simulations. © 2009 American Chemical Society
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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