1,720,972 research outputs found
Quantitative Polypharmacology Profiling Based on a Multifingerprint Similarity Predictive Approach
No full textWe present a new quantitative ligand-based bioactivity prediction approach employing a multifingerprint similarity search algorithm, enabling the polypharmacological profiling of small molecules. Quantitative bioactivity predictions are made on the basis of the statistical distributions of multiple Tanimoto similarity θ values, calculated through 13 different molecular fingerprints, and of the variation of the measured biological activity, reported as ΔpIC50, for all of the ligands sharing a given protein drug target. The application data set comprises as much as 4241 protein drug targets as well as 418 485 ligands selected from ChEMBL (release 25) by employing a set of well-defined filtering rules. Several large internal and external validation studies were carried out to demonstrate the robustness and the predictive potential of the herein proposed method. Additional comparative studies, carried out on two freely available and well-known ligand-target prediction platforms, demonstrated the reliability of our proposed approach for accurate ligand-target matching. Moreover, two applicative cases were also discussed to practically describe how to use our predictive algorithm, which is freely available as a user-friendly web platform. The user can screen single or multiple queries at a time and retrieve the output as a terse html table or as a json file including all of the information concerning the explored similarities to obtain a deeper understanding of the results. High-throughput virtual reverse screening campaigns, allowing for a given query compound the quick detection of the potential drug target from a large collection of them, can be carried out in batch on demand
Effects of Annealing and Residual Solvents on Amorphous P3HT and PBTTT Films
No full textOrganic thin film transistors (OTFT) are metal-insulator-semiconductor field-effect transistors in which the semiconductor is a conjugated organic material. They are the subject of intense industrial research because their fabrication process is less expensive when compared with inorganic TFTs. Among the others, the organic material mostly employed in their construction consists of two semiconductor polymers, namely poly(3-hexylthiophene) (P3HT) and poly(2,5-bis(3-alkylthiophen-2-yl)thieno[3,2-b]thiophene) (PBTTT). Despite the large amount of experimental efforts in the characterization of the electronic properties of these devices, several questions regarding their morphological arrangement in bulk and at interfaces remain wide open. Here, we report results obtained by classical molecular dynamics simulations of P3HT and PBTTT inspired by OTFT fabrication techniques. In particular, we investigate how the annealing fabrication process and the presence of residual solvent molecules left over after spin coating might modify the morphology and the dynamics of the amorphous phase of these two polymers. Simulations of both polymer deposits at 300 K after annealing show an increase in the number of interdigitation events between the alkyl chains of two polymeric macromolecules; moreover, we find that the increased stability of the pi-pi stacking is caused by an improved layering of the films, which may account for the better charge transport properties reported in experiments. Our results strongly suggest that thin semiconductor films are required to boost the performances of the devices and that a minimal presence of residual solvent does not alter dramatically the microscopic structure and stability of the polymeric films
Multitarget Drug Design for Neurodegenerative Diseases
No full textThe quest for new pharmacological treatments of neurodegenerative diseases (NDs) still remains a priority for researchers and caregivers. Being inherently multifactorial, NDs benefited of the paradigm shift from “one-drug-one-target” to “one-drug-more-target” which is typical of the so-called multitarget approach, whose ultimate aim is that of providing a wider pharmacological spectrum to single molecular entities. A multitarget drug should encompass the basic molecular features necessary for an effective interaction with each desired biological target. In this respect, different drug design strategies, mostly inspired by ligand- based and target-based approaches, have been envisaged to achieve this goal. Indeed, huge efforts have been addressed in recent years to harmonically integrate the amount of different (bio)chemical information in the attempt to derive reliable predictive multitarget models. An overview of multitarget computational methods as well as of some successful applications to NDs will be the focus of this chapter
Accelerating drug discovery by early protein drug target prediction based on a multi-fingerprint similarity search †
No full textIn this continuing work, we have updated our recently proposed Multi-fingerprint Similarity Search algorithm (MuSSel) by enabling the generation of dominant ionized species at a physiological pH and the exploration of a larger data domain, which included more than half a million high-quality small molecules extracted from the latest release of ChEMBL (version 24.1, at the time of writing). Provided with a high biological assay confidence score, these selected compounds explored up to 2822 protein drug targets. To improve the data accuracy, samples marked as prodrugs or with equivocal biological annotations were not considered. Notably, MuSSel performances were overall improved by using an object-relational database management system based on PostgreSQL. In order to challenge the real effectiveness of MuSSel in predicting relevant therapeutic drug targets, we analyzed a pool of 36 external bioactive compounds published in the Journal of Medicinal Chemistry from October to December 2018. This study demonstrates that the use of highly curated chemical and biological experimental data on one side, and a powerful multifingerprint search algorithm on the other, can be of the utmost importance in addressing the fate of newly conceived small molecules, by strongly reducing the attrition of early phases of drug discovery programs
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
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