1,720,974 research outputs found
Pharmacophore Modelling: A Forty Year Old Approach and its Modern Synergies
No full textA pharmacophore represents a simple and intuitive concept that can be used in many different drug discovery applications. Ligand-based and structure-based pharmacophore models continue to play a pivotal role in hit discovery and may guide lead optimization. Moreover, owing to the versatility of the pharmacophore concept, pharmacophore modelling has been routinely used in combination with other molecular modelling techniques. The synergistic use of different tools in drug discovery workflows may allow to fully exploit the advantages, while compensating for some of the intrinsic limitations, of each methodology. This review will focus on the synergistic combination of pharmacophore modelling with other molecular modelling approaches such as the hot spot analysis of protein binding sites, molecular dynamics, and docking
Pharmacophore modeling: a continuously evolving tool for computational drug design
No full textIn the latest two or three years progressive
applications of pharmacophore modeling continue to
appear in literature. Pharmacophore based parallel
screening, for instance, has been introduced in 2006.
Moreover, in 2008, a survey discussing the prospective
impact of virtual screening techniques in the
discovery of bioactive natural products has been
published. Finally, virtual screening techniques
from the drug discovery field are beginning to
be used for profiling the bioactivity of chemicals (especially those of potential environmental concern) with the aim of
prioritizing compounds for further testing using more complex systems and
reducing and ultimately replacing the use of animals in regulatory testing.
Pharmacophore modeling might be extremely helpful to allow full
achievement of all the above mentioned goals. In this contribution we report
a couple of case studies where pharmacophore generation and handling
played a pivotal role. In particular, in the first example, the development of a
novel computational pre-screening approach to be used as an in silico
filtering tool for natural products is described, applied to the estrogen
receptor-α subtype. In the second study, differently, the validation of a
preexisting pharmacophore by the prediction of the antifungal activities of
new azole compounds is discussed. In this case, it comes to light the
importance and utility of adding excluded volumes to a pharmacophore, to
increase its predictivity
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
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
A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 to identify new inhibitors of gp120-CD4 protein-protein interactions
No full textA dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 was built and used to identify new hits able to inhibit gp120–CD4 protein–protein interactions. Two compounds showed micromolar inhibition of HIV-1 replication in cells attributable to an interference with the entry step of infection, by direct interaction with gp120. Inactivity of compounds toward a M475I strain suggested specific contacts with the Phe43 cavity of gp120
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