1,720,968 research outputs found
Computation of Standard Binding Free Energies of Polar and Charged Ligands to the Glutamate Receptor GluA2
No full textAccurate calculation of the binding affinity of small molecules to proteins has the potential to become an important tool in rational drug design. In this study, we use the free energy perturbation (FEP) method with restraints to calculate the standard binding free energy of five ligands (ACPA, AMPA, CNQX, DNQX, and glutamate) to the glutamate receptor GluA2, which plays an essential role in synaptic transmission. To deal with the convergence problem in FEP calculations with charged ligands, we use a protocol where the ligand is coupled in the binding site while it is decoupled in bulk solution simultaneously. The contributions from the conformational, rotational, and translational entropies to the standard binding free energy are determined by applying/releasing respective restraints to the ligand in bulk/binding site. We also employ the confine-and-release approach, which helps to resolve convergence problems in FEP calculations. Our results are in good agreement with the experimental values for all five ligands, including the charged ones which are often problematic in FEP calculations. We also analyze the different contributions to the binding free energy of each ligand to GluA2 and discuss the nature of these interactions.Australian Research Counci
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
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
Dinâmica micelar na transição de fases da água
Get PDFDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matermáticas. Programa de Pós-graduação em FísicaEste trabalho visa reproduzir a micelização de anfifílicas em água, realizando simulações computacionais que utilizam o Método de Monte Carlo para estudar as propriedades de uma solução micelar. O modelo escolhido para nosso estudo consiste numa mistura de moléculas de água e anfifílicas numa rede de três dimensões que possui uma geometria cúbica de corpo centrado (BCC). Aqui, as moléculas de água apresentam uma geometria tetraédrica e uma liberdade de reorientação de suas ligações com as suas vizinhas, simulando a formação e destruição de pontes de hidrogênio. A água também possui uma densidade variável, o que possibilita o aparecimento de diferentes fases do solvente para diferentes valores da densidade e da temperatura. As moléculas anfifílicas são representadas por sítios interconectados na rede, estes últimos podendo ter característica hidrofóbica ou hidrofílica. São realizadas simulações utilizando o método de Monte Carlo para diferentes densidades da água e diferentes temperaturas, sendo o foco principal a observação do comportamento de uma solução micelar quando há uma transição de fases do solvente. Diferentes variáveis termodinâmicas da solução - como a concentração micelar crítica (CMC), polidispersividade, constantes de associação e dissociação, tempos de relaxamento e difusão - são analisadas em função da densidade da água para diferentes temperaturas, e é observada uma clara influência da densidade e de uma transição de fases do solvente na dinâmica das micelas. Além disso, é investigada a mudança no comportamento das moléculas do solvente devido à presença das micelas, comparando a liberdade de reorientação de moléculas de água quando na superfície de uma micela e no solvente livre (bulk da solução). Observa-se uma diferença na correlação reorientacional para moléculas de água no bulk e moléculas de água vizinhas a micelas, e também a influência da fase em que o solvente se encontra nessa mesma correlação. Apesar de em nosso modelo as moléculas de água não formarem pontes de hidrogênio com as cabeças polares das anfifílicas, conseguimos reproduzir aqui, a partir de um modelo simples, um comportamento observado em estudos recentes que utilizam dinâmica molecular, que é a diferença na correlação reorientacional para moléculas de água próximas a micelas em relação àquelas do solvente livre
Computational studies of glutamate transporters and receptors
Get PDFIn this thesis we use molecular dynamics simulations to study glutamate transporters and receptors, as well as toxin binding to human potassium channels. We apply a variety of techniques in computational biology such as ligand docking, parameterization of molecules, homology modeling, free energy perturbation and potential of mean force. We first study the archaeal aspartate transporter GltPh, which is a homolog of the human glutamate transporters (EAATs). We locate the third sodium ion binding site and show that this site is also conserved in the EAATs. We then perform molecular dynamics simulations in the outward and inward facing states of GltPh, calculating the ligand affinities in both conformations, the order of ligand binding/unbinding, and the differences in the gating mechanism between the inward and outward states. Using the GltPh crystal structures, we build models for the human glutamate transporters. We use our models to locate the potassium and proton binding sites in EAATs, investigate the gating mechanism, and elucidate the mechanism of proton transport. We also calculate the standard binding free energy of five small molecules to the ligand binding domain of the GluA2 receptor, using a free energy perturbation approach that produces results with very good agreement to experimental values. We show that this method is effective for polar and charged ligands, and can be applied to many biological systems, providing an useful tool in computer aided drug design. Finally, we develop a method based on free energy perturbation that can be used to calculate the binding free energy differences of peptide toxin mutants to Kv potassium channels, producing very good agreement to potential of mean force and experimental results. We use it to obtain a ShK mutant that is selective for the Kv1.1 channel over Kv1.3, and therefore may be used in the treatment of auto-immune diseases
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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