1,720,976 research outputs found
Variable Selection and Interpretation in Structure-Affinity Correlation Modeling of Estrogen Receptor Binders
No full textA computational approach for the identification and investigation of correlations between a chemical structure and a selected biological property is described. It. is based on a set of 132 compounds of known chemical structures, which were tested for their binding affinities to the estrogen receptor. Different multivariate modeling methods, i.e., partial least-squares regression, counterpropagation neural network, and error-back-propagation neural network, were applied, and the prediction ability of each model was tested in order to compare the results of the obtained models. To reduce the extensive set of calculated structural descriptors, two types of variable selection methods were applied, depending on the modeling approach used. In particular, the final partial least-squares regression model was built using the "variable importance in projection" variable selection method, while genetic algorithms were applied in neural network modeling to select the optimal set of descriptors. A thorough statistical study of the variables selected by genetic algorithms is shown. The results were assessed with the aim to get insight to the mechanisms involved in the binding of estrogenic compounds to the receptor. The variable selection oil the basis of genetic algorithm wits controlled with the test set of compounds, extracted from the data set available. To compare the predictive ability of all the optimized models, a leave-one-out cross-validation procedure was applied, the best model being the nonlinear neural network model based on error back-propagation algorithm, which resulted in R-2 = 92.2% and Q(2) = 70.8%
Impact of Mercury(II) on proteinase K catalytic center: investigations via classical and Born-Oppenheimer molecular dynamics
No full textMercury(II) has a strong affinity for the thiol groups in proteins often resulting in the disruption of their biological functions. In this study we present classical and first-principles, DFT-based molecular dynamics (MD) simulations of a complex of Hg(II) and proteinase K, a well-known serine protease with a very broad and diverse enzymatic activity. It contains a catalytic triad formed by Asp39, His69, and Ser224, which is responsible for its biological activity. It was found previously by X-ray diffraction experiments that the presence of Hg(II) inhibits the enzymatic action of proteinase K by affecting the stereochemistry of the triad. Our simulations predict that (i) the overall structure as well as the protein backbone dynamics are only slightly affected by the mercury cation, (ii) depending on the occupied mercury site, the hydrogen bonds of the catalytic triad are either severely disrupted (both bonds for mercury at site 1, and the His69-Ser224 contact for mercury at site 2) or slightly strengthened (the Asp39-His69 bond when mercury is at site 2), (iii) the network of hydrogen bonds of the catalytic triad is not static but undergoes constant fluctuations, which are significantly modified by the presence of the Hg(II) cation, influencing in turn the triad's ability to carry out the enzymatic function-these facts explain the experimental findings on the inhibition of proteinase K by Hg(II)
Structure Elucidation of Transmembrane Proteins using Public-Available Databases and Experimental Data on Competitive Inhibition
No full textWe present an approach towards structure elucidation of bilitranslocase, the membrane protein which transports biliru- bin from blood to liver cells. The sequence and secondary structure information of transmembrane segments of proteins with known 3D structure is exploited to predict the transmembrane domains of structurally unresolved target protein. With the help of known structures the transmembrane domains are encoded in such a way that it is possible to group and classify them with respect to their specific sub-structural characteristics and to build a model for prediction of tran- smembrane segments. We have shown that the model for prediction of transmembrane segments proposed four tran- smembrane alpha helices, each containing around 20 amino acids. This result is partially confirmed with experimental studies using particular antibodies corresponding to parts of amino acid sequences of bilitranslocase. In order to shed light on the bilitranslocase transport mechanism, we also tested a set of non-congeneric compounds for their competiti- ve inhibition constants in the investigated protein-substrate system. The information about chemical structure of small molecules that either pass or block the transmembrane path enabled by bilitranslocase helps us to build a hypothesis about the transport mechanism of the studied biological system
Application of counterpropagation artificial neural network for modelling properties of fish antibiotics
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Properties of flavonoids influencing the binding to bilitranslocase investigated by neural network modelling
No full textBilitranslocase is a plasma membrane carrier firstly identified on the sinusoidal (vascular) domain of liver cells and later on also in the gastric epithelium. It transports diverse organic anions, such as bilirubin, some phthaleins and many dietary anthocyanins, suggesting that it could play a role both in the absorption of flavonoids from dietary sources and in their hepatic metabolism. This work was aimed at characterising the interaction of bilitranslocase with flavonols, a flavonoid sub-class. The results obtained show that, contrary to anthocyanins, flavonol glycosides do not interact with the carrier, whereas just some of the corresponding aglycones act as relatively poor ligands to bilitranslocase. These data point to a clear-cut discrimination between anthocyanins and flavonols occurring at the level of the bilitranslocase transport site. A quantitative structure-activity relationship based on counter propagation artificial neural network modelling was undertaken in order to shed light on the nature of flavonoid interaction with bilitranslocase. It was found that binding relies on the ability to establish hydrogen bonds, ruling out the involvement of charge interactions. This requisite might be at the basis of the discrimination between anthocyanins and flavonols by bilitranslocase and could lie behind some aspects of the distinct pharmacokinetic properties of anthocyanins and flavonols in mammals
Variations on the Author
Full text link“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
Full text linkWe 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
Full text linkWe 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
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