1,720,961 research outputs found
Interplay of stereo-electronic, environmental, and dynamical effects in determining the EPR parameters of aromatic spin-probes: INDCO as a test case
No full textAn integrated computational strategy for the evaluation of reliable structures and magnetic properties of spin probes and spin labels has been extended to aromatic species. From an electronic point of view, delocalization of the unpaired electron density over aromatic moieties reduces significantly the computed nitrogen isotropic hyperfine coupling constant (A(N)) with respect to values characteristic of aliphatic nitroxides. Solvent effects in not too high polarity media are quite small, but not negligible. At this stage computed A(N) are lower than their experimental counterparts by more than 1 G. Inclusion of vibrational averaging effects by molecular dynamics simulations with a new reliable force field restores full agreement with experiment pointing out the limits of static approaches irrespective of the sophistication of the electronic quantum mechanical method. The generality and computational effectiveness of the proposed integrated approach paves the route toward a reliable analysis of the interplay of stereo-electronic, environmental, and dynamical effects in tuning the properties of large flexible magnetic systems of biological and technological interest
Homology building, protein-protein docking and MD approach to the simulation of the quaternary complex E1/E2/Ub2
No full textUbiquitylation is essential to numerous cellular and developmental processes. Alterations in this process are observed in most cancer cells. Ubiquitylation is catalysed by the sequential action of ubiquitin-activating enzyme (UbA1; E1), a ubiquitin-conjugating enzyme (UbC; E2) and a ubiquitin protein ligase (E3). Despite the central role of the E1 enzyme in the Ub conjugation cascade, and its potential as drug target, information regarding the mechanism of UbA1 ubiquitylation or of the Ub transfer from UbA1 to the E2, are limited to mutational studies,[1] and the mechanistic details of ubiquitin thioester bond formation and transfer to substrate are still undetermined. In this context, we have simulated in silico the entire process leading to the UbA1-UbC interaction, by means of a computational approach including many techniques such as homology building, protein-protein docking and molecular dynamics. In particular here we describe static models of hUbA1, as well as of its intermediate complexes involved in the activation and in the formation of transient thiolester complex: i) hUbA1 in complex with adenylated ubiquitin, ii) the covalent adduct between Ub and hUbA1, iii) the hUbA1 in complex with adenylated ubiquitin and covalently linked to the ubiquitin and, finally iv) the quaternary complex including hUbA1 two ubiquitin molecules and a member of the UBC family of enzymes.
In this proposal, we intend to study the conformational behaviour of these four model by using a computational approach characterized by an increased level of accuracy in the study of the system. To the best of our knowledge, this is the first structural information on the hUbA1/E2 complex, and therefore could disclose important information on the mechanism of this important enzyme and will pave the way to the rational design of ubiquitylation inhibitors
Extension of the AMBER force-field for the study of large nitroxides in condensed phases: an ab initio parameterization
No full textThe popular AMBER force-field has been extended to provide an accurate description of large and flexible nitroxide free-radicals in condensed phases. New atom types have been included, and relevant parameters have been fitted based on geometries, vibrational frequencies and potential energy surfaces computed at the DFT level for several different classes of nitroxides, both in vacuo and in different solvents. The resulting computational tool is capable of providing reliable structures, vibrational frequencies, relative energies and spectroscopic observables for large and flexible nitroxide systems, including those typically used as spin labels. The modified force field has been employed in the context of an integrated approach, based on classical molecular dynamics and discrete-continuum solvent models, for the investigation of environmental and short-time dynamic effects on the hyperfine and gyromagnetic tensors of PROXYL, TEMPO and INDCO spin probes. The computed magnetic parameters are in very good agreement with the available experimental values, and the procedure allows for an unbiased evaluation of the role of different effects in tuning the overall EPR observables
Interplay of stereo-electronic, environmental, and dynamical effects in determining the EPR parameters of aromatic spin-probes: INDCO as a test case.
No full textAn integrated computational strategy for the evaluation of reliable structures and magneticproperties of spin probes and spin labels has been extended to aromatic species. From anelectronic point of view, delocalization of the unpaired electron density over aromatic moietiesreduces significantly the computed nitrogen isotropic hyperfine coupling constant (AN) withrespect to values characteristic of aliphatic nitroxides. Solvent effects in not too high polaritymedia are quite small, but not negligible. At this stage computed AN are lower than theirexperimental counterparts by more than 1 G. Inclusion of vibrational averaging effects bymolecular dynamics simulations with a new reliable force field restores full agreement withexperiment pointing out the limits of static approaches irrespective of the sophistication of theelectronic quantum mechanical method. The generality and computational effectiveness of theproposed integrated approach paves the route toward a reliable analysis of the interplay ofstereo-electronic, environmental, and dynamical effects in tuning the properties of large flexiblemagnetic systems of biological and technological interest
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Structural and Dynamic Effects in Physico-chemical Properties of Biomolecules: An Integrated Computational Approach.
No full textIn this thesis we present an integrated computational approach for the accurate prediction of magnetic properties of medium to large molecular systems in vacuo and in condensed phases. The strategy adopted relies on the integration of sophisticated quantum mechanical models with tailored force field methods; the results obtained show that, in the specific context of magnetic parameters, the approach provides answers that are as accurate as even the highest-level full quantum mechanics calculations, at a fraction of the computational cost. In particular, the extension of the popular AMBER force field to medium-large organic free radical nitroxides in vacuo and in condensed phase is presented. New atom types have been introduced whose parameters were fitted on the geometry, vibrational frequencies and potential energy surfaces (PES) derived by density functional theory (DFT) calculations on selected classes of nitroxides. Force field parameterization has been extended to include specific structural features that are often present alongside the paramagnetic center, e.g. in α-amino acidic nitroxides. This required the development of a force-field description for the peptide bonds of strongly helicogenic residues with serious steric restrictions. The resulting molecular mechanical method has been employed in an integrated computational characterization of the role of structural, environmental and short-time dynamic effects in tuning the hyperfine and gyromagnetic tensors of nitroxide spin probes, with results that are quite comparable with the available experimental counterparts
Variations on the Author
Get PDF“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
Get PDFWe 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
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