1,720,991 research outputs found
Thermodynamics of Metal–Acetate Interactions
No full textMetal ions play crucial roles in protein- and ligand-mediated interactions. They not only act as catalysts to facilitate biological processes but are also important as protein structural elements. Accurately predicting metal ion interactions in computational studies has always been a challenge, and various methods have been suggested to improve these interactions. One such method is the 12-6-4 Lennard-Jones (LJ)-type nonbonded model. Using this model, it has been possible to successfully reproduce the experimental properties of metal ions in aqueous solution. The model includes induced dipole interactions typically ignored in the standard 12-6 LJ nonbonded model. In this we expand the applicability of this model to metal ion-carboxylate interactions. Using 12-6-4 parameters that reproduce the solvation free energies of the metal ions leads to an overestimation of metal ion-acetate interactions, thus, prompting us to fine-tune the model to specifically handle the latter. We also show that the standard 12-6 LJ model significantly falls short in reproducing the experimental binding free energy between acetate and 11 metal ions (Ni(II), Mg(II), Cu(II), Zn(II), Co(II), Cu(I), Fe(II), Mn(II), Cd(II), Ca(II), and Ag(I)). In this study, we describe optimized C4 parameters for the 12-6-4 LJ nonbonded model to be used with three widely employed water models (Transferable Intermolecular Potential with 3 Points (TIP3P), Simple Point Charge Extended (SPC/E), and Optimal Point Charge (OPC) water models). These parameters can accurately match the experimental binding free energy between 11 metal ions and acetate. These parameters can be applied to the study of metalloproteins and transition metal ion channels and transporters, as acetate serves as a representative of the negatively charged amino acid side chains from aspartate and glutamate
Computational Study of the Resistance Shown by the Subtype B/HIV-1 Protease to Currently Known Inhibitors
No full textHuman immunodeficiency virus type 1 protease (HIV-1 PR) is an essential
enzyme in the HIV-1 life cycle. As such, this protein represents a major
drug target in AIDS therapy, but emerging resistance to antiretroviral
inhibitor cocktails, caused by high viral mutation rates, represents a
significant challenge in AIDS treatment. Many mutations are not located
within the active site or binding pocket, nor they do significantly
modify the three-dimensional structural organization of the enzyme;
hence, the mechanism(s) by which they alter inhibitor affinity for the
protease remains uncertain. In this article, we present an all-atom
computational analysis of the dynamic residue-residue coordination
between the active site residues and the rest of the protein and of the
energetic properties of different HIV-1 PR complexes. We analyze both
the wildtype form and mutated forms that induce drug resistance, In
particular, the results show differences between the wild type and the
mutants in their mechanism of dynamic coordination, in the signal
propagation between the active site residues and the rest of the
protein, and in the energy networks responsible for the stabilization of
the bound inhibitor conformation. Finally, we propose a dynamic and
energetic explanation for HIV-1 protease drug resistance, and, through
this model, we identify a possible new site that could be helpful in the
design of a new family of HIV-1 PR allosteric inhibitors
Simulating Metal-Imidazole Complexes
Full text linkOne commonly observed binding motif in metalloproteins involves the interaction between a metal ion and histidine’s imidazole side chains. Although previous imidazole-M(II) parameters established the flexibility and reliability of the 12-6-4 Lennard-Jones (LJ)-type nonbonded model by simply tuning the ligating atom’s polarizability, they have not been applied to multiple-imidazole complexes. To fill this gap, we systematically simulate multiple-imidazole complexes (ranging from one to six) for five metal ions (Co(II), Cu(II), Mn(II), Ni(II), and Zn(II)) which commonly appear in metalloproteins. Using extensive (40 ns per PMF window) sampling to assemble free energy association profiles (using OPC water and standard HID imidazole charge models from AMBER) and comparing the equilibrium distances to DFT calculations, a new set of parameters was developed to focus on energetic and geometric features of multiple-imidazole complexes. The obtained free energy profiles agree with the experimental binding free energy and DFT calculated distances. To validate our model, we show that we can close the thermodynamic cycle for metal-imidazole complexes with up to six imidazole molecules in the first solvation shell. Given the success in closing the thermodynamic cycles, we then used the same extended sampling method for six other metal ions (Ag(I), Ca(II), Cd(II), Cu(I), Fe(II), and Mg(II)) to obtain new parameters. Since these new parameters can reproduce the one-imidazole geometry and energy accurately, we hypothesize that they will reasonably predict the binding free energy of higher-level coordination numbers. Hence, we did not extend the analysis of these ions up to six imidazole complexes. Overall, the results shed light on metal-protein interactions by emphasizing the importance of ligand-ligand interaction and metal-π-stacking within metalloproteins
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
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