1,721,053 research outputs found
Structural basis of dimerization of chemokine receptors CCR5 and CXCR4
No full textThis is the minimum dataset of the Nature Communication paper "Structural basis of dimerization of chemokine receptors CCR5 and CXCR4".
This repository is composed of two zipped archives.
The first archive, "Dataset Minimum", contains all the trajectories, force field parameters, input files and analyses generated for this work. All relevant information about the specific nature and content of the files in the dataset and its organization is reported in the README files provided inside it.
The second archive, "Source Data", contains only the raw data used to assemble the figures shown in the work. This data is also stored in the Dataset Minimum archive. The files are divided into different folders according to the image they belong to. Each folder is divided into subfolders to distinguish the data reported in each image panel. Most files can be read using Excel or a word processor such as WordPad, NotePad, or Notepad++. Structure files are provided in the pdb format and can be read using software like VMD, Pymol, or Chimera.
Abstract
G protein coupled receptors (GPCRs) are prominent drug targets responsible for extracellular-to-intracellular signal transduction. GPCRs can form functional dimers that have been poorly characterized so far. Here, we show the dimerization mechanism of the chemokine receptors CCR5 and CXCR4 by means of an advanced free-energy technique named coarse-grained metadynamics. Our results reproduce binding events between the GPCRs occurring in the minute timescale - the longest ever simulated - which reveal a symmetric and an asymmetric dimeric structure for each of the three investigated systems, CCR5/CCR5, CXCR4/CXCR4 and CCR5/CXCR4. The transmembrane helices TM4-TM5 and TM6-TM7 are the preferred binding interfaces for CCR5 and CXCR4, respectively. The identified dimer states differ in the access to the binding sites of the ligand and G protein, indicating that dimerization represents a fine allosteric mechanism to regulate receptor activity. Our study offers unprecedented structural bases for the design of ligands able to modulate the formation of CCR5 and CXCR4 dimers and in turn their activity, with therapeutic potential against HIV, cancer and immune-inflammatory diseases.This work has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme ("CoMMBi" ERC grant agreement No.101001784). V.L. especially acknowledges the multi-year support by a grant from the Swiss National Supercomputing Centre (CSCS) under project IDs s1150 and u8, while the funding from "Partnership for Advanced Computing in Europe" (PRACE) (call 16 with project ID 2016153685) was discontinued only after the first year based on the decision of the 2018 PRACE Access Committee and PRACE Board of Directors, which caused delay in research. We also thank the NVIDIA Corporation for the donation of a Tesla K40 GPU. D.D. acknowledges the support of the Italian Foundation for Cancer Research AIRC (Project No. IG 2022 ID 27534)
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
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
Ligand Binding to Telomeric DNA G-quadruplex through Metadynamics Calculations
No full textTelomeres are DNA-proteins complexes which protect the ends of human chromosomes. Telomeric DNA consists of repetitive Guanine-rich (G-rich) sequences which can fold into unusual structural motifs termed G-quadruplexes (G4). In recent times, DNA G4 have emerged as promising targets in anticancer therapy since G4 ligands are able to promote apoptosis in tumor cells. Most of G4 binders are end-stackers whose clinical use is hampered by poor drug-like properties and weak selectivity. Such properties are instead improved in G4 groove binders. Among these, 3-benzothiazol-2-yl-7-hydroxy-8-{[4-(2-hydroxyethyl)piperazinyl]methyl}chrom-en-2-one has been identified as a potent groove binder of the G4 [d(TGGGGT)]4. Here we have set up a metadynamics-based protocol to disclose at molecular level the binding mechanism of this compound to the G4 [d(TGGGGT)]4. Our approach has allowed dealing with target flexibility and solvation during ligand binding and computing the binding free energy of the ligand/DNA G4 complex. Finally, once the binding free energy surface was converged, the lowest energy binding modes have been identified. Our computational protocol is of valuable help for future studies on ligand/DNA interaction and the development of new potent and selective DNA binders
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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